Cilagicin compounds and methods of use thereof

Abstract

The present invention provides methods, compositions, and articles of manufacture useful for treatment of multidrug-resistant pathogens and related conditions. The present invention provides compositions and methods incorporating and utilizing cilagicin compounds or derivatives or variants thereof.

Description

[0001] Attorney Docket No.046531-5034-00WO TITLE OF THE INVENTION CILAGICIN COMPOUNDS AND METHODS OF USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application Serial No. 63 / 634,001, filed April 15, 2024, the disclosure of which is hereby incorporated by reference herein in its entirety. STATEMENT OF GOVERNMENT FUNDING This invention was made with government support under R35GM122559 awarded by the National Institutes of Health. The government has certain rights in the invention. REFERENCE TO SEQUENCE LISTING DESCRIPTION OF THE XML FILE SUBMITTED ELECTRONICALLY The Sequence Listing written in the XML file: “046531-5034- 00US_SequenceListing.xml”; created on April 15, 2025, and 43,511 bytes in size, is hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION Antibiotic resistant infections are a growing public health threat and therefore new antibiotics capable of circumventing existing resistance mechanisms are essential to combat these infections (Pei S. et al., 2023, Emerg Infect Dis, 29:679-685). Bacterial natural products (NPs) have historically been a rich source of antibiotics with diverse modes of actions (Newman D. J. et al., 2020, J Nat Prod, 83:770-803). Unfortunately, accessing microbial NPs from their native producers is hampered by a lack of expression of most biosynthetic gene clusters (BGCs) under laboratory conditions (Bodor A. et al., 2020, Rev Environ Sci Bio, 19:1-22; Covington B. C. et al., 2021, Annu Rev Biochem, 90:763-788). Thus, there is a need in the art for new compounds, compositions, and methods for treating infections. The present invention satisfies this unmet need in the art. SUMMARY OF THE INVENTION In one aspect, the present invention relates to a compound comprising the structure of Formula (I): Attorney Docket No.046531-5034-00WO or a acceptable salt, or a derivative thereof. In some embodiments, X is selected from the group consisting of O, S, and N(R14). In some embodiments, each occurrence of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14is independently selected from the group consisting of hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof. In some embodiments, m is an integer from 0 to 100. In some embodiments, the compound comprises the structure of Formula (II)

[0002] Attorney Docket No.046531-5034-00WO or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof. In some embodiments, R1, R2, R3, and R4are each independently selected from the group consisting of hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof. In some embodiments, L represents a group of the formula -C(O)(CH2)p-(Y)q-(CH2)r- H. In some embodiments, q and r independently represent an integer having a value between 1 and 20. In some embodiments, q represents 0 or 1. In some embodiments, Y represents cis or trans -C(H)=C(H)-. In some embodiments, the compound comprises the structure of Formula (IIa) or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof. In some embodiments, the compound comprises the structure of Formula (III) Attorney Docket No.046531-5034-00WO or a racemate, an a a salt, or a derivative thereof. In some embodiments, R1is selected from the group consisting of hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof. In some embodiments, the compound comprises the structure of Formula (IIIa)

[0003] Attorney Docket No.046531-5034-00WO or a racemate, an a a salt, or a derivative thereof. In one embodiment, m is an integer represented by 0. In one embodiment, m is an integer represented by 1. In one embodiment, the compound is a zwitterion. In one embodiment, the zwitterion comprises at least two positively charged residues and at least two negatively charged residues. In one embodiment, the compound comprises at least one amino acid sequence selected from at least one amino acid sequence as set forth in SEQ ID NO: 1-49, amino acid sequence from Figure 2A, at least one amino acid sequence selected from Figure 4A, at least one selected from Figure 6, or any combination thereof. In one embodiment, the compound comprises one of the following compounds, or any racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or derivative thereof: , Attorney Docket No.046531-5034-00WO , O , the compound specifically binds at least one undecaprenyl phosphorylate, undecaprenyl pyrophosphate, or a combination thereof. In another aspect, the present invention relates to an isolated nucleic acid molecule encoding at least one inventive compound. In one aspect, the invention relates to a genetically engineered cell capable of producing at least one inventive compound. In one aspect, the invention relates to a composition comprising at least one inventive compound, at least one nucleic acid molecule encoding at least one inventive compound, or at least one genetically Attorney Docket No.046531-5034-00WO engineered cell capable of producing at least one inventive compound. In one embodiment, the composition is a pharmaceutical composition. In one aspect, the present invention relates to method of treating or preventing a bacterial infection in a subject in need thereof, the method comprising administering at least one inventive compound, at least one nucleic acid molecule encoding at least one inventive compound, or at least one genetically engineered cell capable of producing at least one inventive compound. In one embodiment, the subject is exposed to or infected with a pathogen. In one embodiment, the pathogen is selected from any pathogen listed in Figure 6, Table 1, Table 6, or any combination thereof. In one embodiment, the pathogen is bacteria. In one embodiment, the bacteria is selected from the group consisting of drug resistant bacteria, gram positive bacteria, and any combination thereof. In one embodiment, the bacteria is selected from the group consisting of Bacillus subtilis, Clostridium difficile, Enterococcus faecium, Enterococcus gallinarum, Enterococcus casseliflavus, Escherichia coli, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyrogens, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, Enterobacter species, and any combination thereof. In one embodiment, the method further comprises administering a second therapeutic. In one embodiment, the second therapeutic is an antibiotic. In one aspect, the present invention relates to a method of inhibiting the growth of or killing a bacterial cell, the method comprising, contacting the bacterial cell with at least one inventive compound, at least one nucleic acid molecule encoding at least one inventive compound, or at least one genetically engineered cell capable of producing at least one inventive compound. In one aspect, the present invention relates to a method of biosynthesizing at least one inventive compound, the method comprising: a) providing a nucleic acid to a host or a growth medium, b) incubating the host in a growth medium; and c) isolating the compound from the host or the growth medium. BRIEF DESCRIPTION OF THE DRAWINGS The following detailed description of preferred embodiments of the present invention will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings embodiments which are presently preferred. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings. Attorney Docket No.046531-5034-00WO Figure 1 depicts a representative schematic illustration of the discovery approach used in the present study. Figure 2, comprising Figure 2A and Figure 2B, depicts a schematic representation of Cilagicin (1), a dual polyprenyl phosphate binding antibiotic. Figure 2A depicts a schematic representation of a molecular structure of cilagicin and cilagicin (cil) BGC. Substrate generations for each A-domain in the cil BGC are also shown. Figure 2B depicts a schematic representation of structures of polyprenyl phosphates C55:P and C55:PP Figure 3, comprising Figure 3A and Figure 3B, depicts a schematic representation of the search of generated non-ribosomal polypeptide synthetase (NRPS) structures for antibiotics that evade resistance. Figure 3A depicts a schematic representation of the summary of bioinformatic approach used to identify BGCs of interest. Sequenced NRPS BGCs were collected from publicly available genome databases. Clusters without clearly defined start domains (Cs and CAL) and termination domains (TE) were removed because both are required for cilagicin-like structures. Linear peptide sequences from each complete NRPS BGCs were generated using A-Domain signatures. Resultant generations were ranked by their identity to the linear sequence of cilagicin. Figure 3B depicts representative three BGCs that were generated to encode linear NRPS that are >50% identical to the sequence of cilagicin. Figure 4, comprising Figure 4A and Figure 4B, depicts a schematic representation of natural product (NP) structure generations. Figure 4A depicts representative domain composition and A-domain analysis [CoA-ligase (CAL), phosphopantetheine-binding (PP), ketosynthase (KS), acyl transferase (AT), adenylation (A), condensation (C), thiolation (T), epimerization (E), thioesterase (TE)]. Figure 4B depicts a schematic representation of representative final structures generated to arise from each BGC. Variable (red) and conserved (green) regions are highlighted. Figure 5, comprising Figure 5A and Figure 5B, depicts representative results demonstrating suppression of antibiotic activity by polyprenyl phosphates and development of resistance in serially passaged cultures. Figure 5A depicts representative results demonstrating MICs of antibiotic against S. aureus in the presence of different molar ratios of C55:P or C55:PP. The highest concentration of peptide tested was 64 ug / mL. Average of two replicate experiments with error bars representing standard deviation. Figure 5B depicts representative results demonstrating fold change in MIC from Day 0 to Day 14 of each synBNP against serially passed S. aureus cultures exposed 0.5x MIC of the same antibiotic. Figure 6 depicts representative NRPS structure generation database search results of Attorney Docket No.046531-5034-00WO BGCs. Figure 7, comprising Figure 7A through Figure 7C, depicts representative results of LC-MS analysis of natural cilagicin analog synBNPs. HPLC chromatogram (top) and High- resolution mass spectra (bottom). Figure 7A depicts representative results of LC-MS analysis of Paenilagicin. Figure 7B depicts representative results of LC-MS analysis of bacilagicin. Figure 7C depicts representative results of LC-MS analysis of Virgilagicin. Figure 8, comprising Figure 8A through Figure 8C, depicts representative results of MS-MS analysis of Paenilagicin. Figure 8A depicts representative results demonstrating parent ions of Paenilagicin. Figure 8B depicts representative results demonstrating assignment of MS / MS fragment ions of Paenilagicin. Figure 8C depicts schematic representation of structures of MS / MS fragment ions of Paenilagicin, chemical formula, and theoretical m / z. Figure 9, comprising Figure 9A through Figure 9C, depicts representative results of MS-MS analysis of Bacilagicin. Figure 9A depicts representative results demonstrating parent ions of Bacilagicin. Figure 9B depicts representative results demonstrating assignment of MS / MS fragment ions of Bacilagicin. Figure 9C depicts schematic representation of structures of MS / MS fragment ions of Bacilagicin, chemical formula, and theoretical m / z. Figure 10, comprising Figure 10A through Figure 10C, depicts representative results of MS-MS analysis of Virgilagicin. Figure 10A depicts representative results demonstrating parent ions of Virgilagicin. Figure 10B depicts representative results demonstrating assignment of MS / MS fragment ions of Virgilagicin. Figure 10C depicts schematic representation of structures of MS / MS fragment ions of Virgilagicin, chemical formula, and theoretical m / z. Figure 11, comprising Figure 11A and Figure 11B, depicts representative1H and13C NMR spectra of Paenilagicin. Figure 11A depicts a representative1H spectrum of Paenilagicin (DMSO-d6, 600MHz). Figure 11B depicts a representative13C spectrum of Paenilagicin (DMSO-d6, 150MHz). Figure 12, comprising Figure 12A and Figure 12B, depicts representative1H and13C NMR spectra of Bacilagicin. Figure 12A depicts a representative1H spectrum of Bacilagicin (DMSO-d6, 600MHz). Figure 12B depicts a representative13C spectrum of Bacilagicin (DMSO-d6, 150MHz). Figure 13, comprising Figure 13A and Figure 13B, depicts representative1H and13C NMR spectra of Virgilagicin. Figure 13A depicts a representative1H spectrum of Virgilagicin (DMSO-d6, 600MHz). Figure 13B depicts a representative13C spectrum of Attorney Docket No.046531-5034-00WO Virgilagicin (DMSO-d6, 150MHz). Figure 14 depicts representative experimental results for exemplary compounds of the present invention. Figure 15 depicts a schematic representation of a summary of residue mutations for cilagicin. Figure 16 depicts representative results demonstrating activities of various replacements for the lipophilic chain of cilagicin. Figure 17 depicts representative in vitro results for dodecacilagicin and cilagicin-BP. Figure 18 depicts representative results demonstrating plasma protein binding of dodecacilagicin and cilagicin-BP. Figure 19 depicts representative results demonstrating the CYP inhibition of dodecacilagicin. Figure 20 depicts representative results demonstrating the CYP inhibition of cilagicin- BP. Figure 21 depicts representative results demonstrating hERG+ assay of dodecacilagicin and cilagicin-BP. Figure 22 depicts representative results of metabolism profiling for dodecacilagicin. Figure 23 depicts representative XIS of full MS scan for dodecacilagicin. Five metabolites were detected in human hepatocytes samples. Figure 24 depicts a schematic representation of metabolite identification in human hepatocytes by dodecacilagicin. Figure 25 depicts representative results of metabolism profiling for cilagicin-BP. Figure 26 depicts representative XIS of full MS scan for cilagicin-BP. Seven metabolites were detected in human hepatocytes samples. Figure 27 representative results of metabolism profiling for cilagicin-BP using LC- UV chromatogram (274 nm, human hepatocytes). Figure 28 depicts a schematic representation of metabolite identification in human hepatocytes by cilagicin-BP. Figure 29 depicts representative results demonstrating pharmacokinetics of dodecacilagicin PK. Figure 30 depicts representative results of comparison mouse efficacy model. Figure 31 depicts representative results of mouse MTD study. DETAILED DESCRIPTION Attorney Docket No.046531-5034-00WO The present invention is based, in part, on the unexpected discovery of cilagicin compounds as antibiotics which have activity against multidrug resistant pathogens. In one aspect, the present invention provides compounds or a therapeutic compound comprising a desired activity. In one embodiment, the compound is an antibiotic. In one embodiment, the antibiotic compound of the present invention can be used in the treatment of bacterial infections. In one embodiment, the antibiotic compound of the present invention can be used in the treatment of gram positive bacterial infections. In certain embodiments, the use of the antibiotic compound of the present invention in the treatment of bacterial infections optionally includes a pharmaceutically acceptable carrier, excipient, or adjuvant. In one embodiment, the compound can be biosynthesized via heterologous expression of a biosynthetic gene. Thus, in one aspect, the invention provides compounds and methods for synthesizing cilagicin compounds. In one embodiment, the invention provides a nucleic acid encoding cilagicin compounds. In one embodiment, the nucleic acid is an isolated nucleic acid. In one embodiment, the nucleic acid is transformed into a cell. Definitions Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described. As used herein, each of the following terms has the meaning associated with it in this section. The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the of the article. By way of example, “an element” means one element or more than one element. “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods. A “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal’s health continues to deteriorate. In contrast, a “disorder” in an animal is a state of health in which the animal is able to Attorney Docket No.046531-5034-00WO maintain homeostasis, but in which the animal’s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal’s state of health. A disease or disorder is “alleviated” if the severity of a sign or symptom of the disease or disorder, the frequency with which such a sign or symptom is experienced by a patient, or both, is reduced. To “treat” a disease as the term is used herein, means to reduce the frequency or severity of at least one sign or symptom of a disease or disorder experienced by a subject. The terms “patient,” “subject,” “individual,” and the like are used interchangeably herein, and refer to any animal, or cells thereof whether in vitro or in situ, amenable to the methods described herein. In certain non-limiting embodiments, the patient, subject or individual is a human. “Parenteral” administration of a composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques. The term “polynucleotide” as used herein is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Thus, nucleic acids and polynucleotides as used herein are interchangeable. One skilled in the art has the general knowledge that nucleic acids are polynucleotides, which can be hydrolyzed into the monomeric “nucleotides.” The monomeric nucleotides can be hydrolyzed into nucleosides. As used herein polynucleotides include, but are not limited to, all nucleic acid sequences which are obtained by any means available in the art, including, without limitation, recombinant means, i.e., the cloning of nucleic acid sequences from a recombinant library or a cell genome, using ordinary cloning technology and PCR™, and the like, and by synthetic means. The term, “biologically active” or “bioactive” can mean, but is in no way limited to, the ability of an agent or compound to effectuate a physiological change or response. The response may be detected, for example, at the cellular level, for example, as a change in growth and / or viability, gene expression, protein quantity, protein modification, protein activity, or combination thereof; at the tissue level; at the systemic level; or at the organism level. For example, as used herein, biologically active molecules include but are not limited to any substance intended for diagnosis, cure, mitigation, treatment, or prevention of disease in humans or other animals, or to otherwise enhance physical or mental well-being of humans or animals. Examples of biologically active molecules include, but are not limited to, peptides, proteins, enzymes, small molecule drugs, dyes, lipids, nucleosides, Attorney Docket No.046531-5034-00WO oligonucleotides, cells, viruses, liposomes, microparticles and micelles. Classes of biologically active agents that are suitable for use with the invention include, but are not limited to, antibiotics, fungicides, anti-viral agents, anti-inflammatory agents, anti-tumor agents, cardiovascular agents, anti-anxiety agents, hormones, growth factors, steroidal agents, and the like. “Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA. An “effective amount” or “therapeutically effective amount” of a compound is that amount of compound which is sufficient to provide a beneficial effect to the subject to which the compound is administered. An “effective amount” of a delivery vehicle is that amount sufficient to effectively bind or deliver a compound. “Homologous” refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. When a position in both of the two compared sequences is occupied by the same base or amino acid monomer subunit, e.g., if a position in each of two DNA molecules is occupied by adenine, then the molecules are homologous at that position. The percent of homology between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the number of positions compared X 100. For example, if 6 of 10 of the positions in two sequences are matched or homologous then the two sequences are 60% homologous. By way of example, the DNA sequences ATGG and ATCC share 50% homology. Generally, a comparison is made when two sequences are aligned to give maximum homology. “Isolated” means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not “isolated,” but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is “isolated.” An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell. Attorney Docket No.046531-5034-00WO Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s). As used herein, the terms “amino acid”, “amino acidic monomer”, or “amino acid residue” refer to any of the twenty naturally occurring amino acids including synthetic amino acids with unnatural side chains and including both D and L optical isomers. In the context of the present invention, term “natural amino acid” means any amino acid which is found naturally in vivo in a living being. Natural amino acids therefore include amino acids coded by mRNA incorporated into proteins during translation but also other amino acids found naturally in vivo which are a product or by-product of a metabolic process, such as for example ornithine which is generated by the urea production process by arginase from L-arginine. In the invention, the amino acids used can therefore be natural or not. Namely, natural amino acids generally have the L configuration but also, according to the invention, an amino acid can have the L or D configuration. A “non-naturally encoded amino acid” refers to an amino acid that is not one of the 20 common amino acids or pyrolysine or selenocysteine. The term “non-naturally encoded amino acid” includes, but is not limited to, amino acids that occur naturally by modification of a naturally encoded amino acid (including but not limited to, the 20 common amino acids or pyrolysine and selenocysteine) but are not themselves incorporated into a growing polypeptide chain by the translation complex. Examples of naturally-occurring amino acids that are not naturally-encoded include, but are not limited to, N-acetylglucosaminyl-L-serine, N-acetylglucosaminyl-L-threonine, and O-phosphotyrosine. As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein’s or peptide’s sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, Attorney Docket No.046531-5034-00WO heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof. Furthermore, peptides of the present invention may include amino acid mimentics, and analogs. Recombinant forms of the peptides can be produced according to standard methods and protocols which are well known to those of skill in the art, including for example, expression of recombinant proteins in prokaryotic and / or eukaryotic cells followed by one or more isolation and purification steps, and / or chemically synthesizing peptides or portions thereof using a peptide sythesizer. The term “pharmacological composition,” “therapeutic composition,” “therapeutic formulation” or “pharmaceutically acceptable formulation” can mean, but is in no way limited to, a composition or formulation that allows for the effective distribution of an agent provided by the invention, which is in a form suitable for administration to the physical location most suitable for their desired activity, e.g., systemic administration. Non-limiting examples of agents suitable for formulation with the, e.g., compounds provided by the instant invention include: cinnamoyl, PEG, phospholipids or lipophilic moieties, phosphorothioates, P-glycoprotein inhibitors (such as Pluronic P85) which can enhance entry of drugs into various tissues, for example the CNS (Jolliet-Riant and Tillement, 1999, Fundam. Clin. Pharmacol., 13, 16-26); biodegradable polymers, such as poly (DL-lactide-coglycolide) microspheres for sustained release delivery after implantation (Emerich, D F et al, 1999, Cell Transplant, 8, 47-58) Alkermes, Inc. Cambridge, Mass.; and loaded nanoparticles, such as those made of polybutylcyanoacrylate, which can deliver drugs across the blood brain barrier and can alter neuronal uptake mechanisms (Prog Neuropsychopharmacol Biol Psychiatry, 23, 941-949, 1999). The term “pharmaceutically acceptable” or “pharmacologically acceptable” can mean, but is in no way limited to, entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal, or a human, as appropriate. The term “pharmaceutically acceptable carrier” or “pharmacologically acceptable carrier” can mean, but is in no way limited to, any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington’s Pharmaceutical Sciences, a standard reference text in the field, which is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, finger’s solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also Attorney Docket No.046531-5034-00WO be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions. A “therapeutic” treatment is a treatment administered to a subject who exhibits signs of pathology, for the purpose of diminishing or eliminating those signs. As used herein, “treating a disease or disorder” means reducing the frequency with which a symptom of the disease or disorder is experienced by a patient. Disease and disorder are used interchangeably herein. The phrase “therapeutically effective amount,” as used herein, refers to an amount that is sufficient or effective to prevent or treat (delay or prevent the onset of, prevent the progression of, inhibit, decrease or reverse) a disease or condition, including alleviating symptoms of such diseases. The term “compound,” as used herein, unless otherwise indicated, refers to any specific chemical compound disclosed herein. In one embodiment, the term also refers to stereoisomers and / or optical isomers (including racemic mixtures) or enantiomerically enriched mixtures of disclosed compounds. As used herein, “derivatives” are compositions formed from the native compounds either directly, by modification, or by partial substitution. As used herein, “analogs” are compositions that have a structure similar to, but not identical to, the native compound. As used herein, the term “alkyl,” by itself or as part of another substituent means, unless otherwise stated, a straight or branched chain hydrocarbon having the number of carbon atoms designated (i.e. C1-6means one to six carbon atoms) and includes straight, branched chain, or cyclic substituent groups. Examples include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n- hexyl, n-heptyl, n-octyl, and the like. The term “alkyl,” unless otherwise noted, is also meant to include those derivatives of alkyl defined in more detail below, such as “heteroalkyl”, “haloalkyl” and “homoalkyl”. As used herein, the term “substituted alkyl” means alkyl, as defined above, substituted by one, two or three substituents selected from the group consisting of halogen, -OH, alkoxy, -NH2, -N(CH3)2, -C(=O)OH, trifluoromethyl, -C≡N, -C(=O)O(C1-C4)alkyl, -C(=O)NH2, - SO2NH2, -C(=NH)NH2, and -NO2, preferably containing one or two substituents selected from halogen, -OH, alkoxy, -NH2, trifluoromethyl, -N(CH3)2, and -C(=O)OH, more Attorney Docket No.046531-5034-00WO preferably selected from halogen, alkoxy and -OH. Examples of substituted alkyls include, but are not limited to, 2,2-difluoropropyl, 2-carboxycyclopentyl and 3-chloropropyl. As used herein, the term “alkylene” by itself or as part of another molecule means a divalent radical derived from an alkane, as exemplified by (-CH2-)n. By way of example only, such groups include, but are not limited to, groups having 24 or fewer carbon atoms such as the structures -CH2CH2- and -CH2CH2CH2CH2-. The term “alkylene,” unless otherwise noted, is also meant to include those groups described below as “heteroalkylene.” As used herein, the terms “alkoxy,” “alkylamino” and “alkylthio” are used in their conventional sense, and refer to alkyl groups linked to molecules via an oxygen atom, an amino group, a sulfur atom, respectively. As used herein, the term “alkoxy” employed alone or in combination with other terms means, unless otherwise stated, an alkyl group having the designated number of carbon atoms, as defined above, connected to the rest of the molecule via an oxygen atom, such as, for example, methoxy, ethoxy, 1-propoxy, 2-propoxy (isopropoxy) and the higher homologs and isomers. Preferred are (C1-C3) alkoxy, particularly ethoxy and methoxy. As used herein, the term “halo” or “halogen” alone or as part of another substituent means, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom, preferably, fluorine, chlorine, or bromine, more preferably, fluorine or chlorine. As used herein, the term “cycloalkyl” refers to a mono cyclic or polycyclic non- aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. In one embodiment, the cycloalkyl group is saturated or partially unsaturated. In another embodiment, the cycloalkyl group is fused with an aromatic ring. Cycloalkyl groups include groups having from 3 to 10 ring atoms. Illustrative examples of cycloalkyl groups include, but are not limited to, the following moieties: . cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Dicyclic cycloalkyls include, but are Attorney Docket No.046531-5034-00WO not limited to, tetrahydronaphthyl, indanyl, and tetrahydropentalene. Polycyclic cycloalkyls include adamantine and norbornane. The term cycloalkyl includes “unsaturated nonaromatic carbocyclyl” or “nonaromatic unsaturated carbocyclyl” groups, both of which refer to a nonaromatic carbocycle as defined herein, which contains at least one carbon carbon double bond or one carbon carbon triple bond. As used herein, the term “heteroalkyl” by itself or in combination with another term means, unless otherwise stated, a stable straight or branched chain alkyl group consisting of the stated number of carbon atoms and one or two heteroatoms selected from the group consisting of O, N, Si, P, and S, and wherein the nitrogen and sulfur atoms may be optionally oxidized and the nitrogen heteroatom may be optionally quaternized. The heteroatom(s) may be placed at any position of the heteroalkyl group, including between the rest of the heteroalkyl group and the fragment to which it is attached, as well as attached to the most distal carbon atom in the heteroalkyl group. Examples include: -O-CH2-CH2-CH3, -CH2-CH2-CH2-OH, -CH2-CH2-NH-CH3, -CH2-S-CH2-CH3, and -CH2CH2-S(=O)-CH3. Up to two heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3, or -CH2-CH2-S-S-CH3. As used herein, the term “heterocycle” or “heterocyclyl” or “heterocyclic” by itself or as part of another substituent means, unless otherwise stated, an unsubstituted or substituted, stable, mono- or multi-cyclic heterocyclic ring system that consists of carbon atoms and at least one heteroatom selected from the group consisting of N, O, and S, and wherein the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen atom may be optionally quaternized. The heterocyclic system may be attached, unless otherwise stated, at any heteroatom or carbon atom that affords a stable structure. A heterocycle may be aromatic or non-aromatic in nature. An example of a 3-membered heterocycloalkyl group includes, and is not limited to, aziridine. Examples of 4-membered heterocycloalkyl groups include, and are not limited to, azetidine and a beta lactam. Examples of 5-membered heterocycloalkyl groups include, and are not limited to, pyrrolidine, oxazolidine and thiazolidinedione. Examples of 6-membered heterocycloalkyl groups include, and are not limited to, piperidine, morpholine and piperazine. Other non-limiting examples of heterocycloalkyl groups are: Attorney Docket No.046531-5034-00WO . as aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, pyrroline, imidazoline, pyrazolidine, dioxolane, sulfolane, 2,3-dihydrofuran, 2,5-dihydrofuran, tetrahydrofuran, thiophane, piperidine, 1,2,3,6-tetrahydropyridine, 1,4-dihydropyridine, piperazine, morpholine, thiomorpholine, pyran, 2,3-dihydropyran, tetrahydropyran, 1,4-dioxane, 1,3-dioxane, homopiperazine, homopiperidine, 1,3-dioxepane, 4,7-dihydro-1,3-dioxepin and hexamethyleneoxide. As used herein, the term “aromatic” refers to a carbocycle or heterocycle with one or more polyunsaturated rings and having aromatic character, i.e. having (4n + 2) delocalized π (pi) electrons, where n is an integer. As used herein, the term “aryl,” employed alone or in combination with other terms, means, unless otherwise stated, a carbocyclic aromatic system containing one or more rings (typically one, two or three rings) wherein such rings may be attached together in a pendent manner, such as a biphenyl, or may be fused, such as naphthalene. Examples include phenyl, anthracyl, and naphthyl. Preferred are phenyl and naphthyl, most preferred is phenyl. As used herein, the term “aryl-(C1-C4)alkyl” means a functional group wherein a one to three carbon alkylene chain is attached to an aryl group, e.g., -CH2CH2-phenyl. Preferred is aryl-CH2- and aryl-CH(CH3)-. The term “substituted aryl-(C1-C4)alkyl” means an aryl-(C1-C4)alkyl functional group in which the aryl group is substituted. Preferred is substituted aryl(CH2)-. Similarly, the term “heteroaryl-(C1-C4)alkyl” means a functional group wherein a one to three carbon alkylene chain is attached to a heteroaryl group, Attorney Docket No.046531-5034-00WO e.g., -CH2CH2-pyridyl. Preferred is heteroaryl-(CH2)-. The term “substituted heteroaryl-(C1-C4)alkyl” means a heteroaryl-(C1-C4)alkyl functional group in which the heteroaryl group is substituted. Preferred is substituted heteroaryl-(CH2)-. Examples of heteroaryl groups include pyridyl, pyrazinyl, pyrimidinyl (particularly 2- and 4-pyrimidinyl), pyridazinyl, thienyl, furyl, pyrrolyl (particularly 2-pyrrolyl), imidazolyl, thiazolyl, oxazolyl, pyrazolyl (particularly 3- and 5-pyrazolyl), isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl. Examples of polycyclic heterocycles include indolyl (particularly 3-, 4-, 5-, 6- and 7-indolyl), indolinyl, quinolyl, tetrahydroquinolyl, isoquinolyl (particularly 1- and 5-isoquinolyl), 1,2,3,4-tetrahydroisoquinolyl, cinnolinyl, quinoxalinyl (particularly 2- and 5-quinoxalinyl), quinazolinyl, phthalazinyl, 1,8-naphthyridinyl, 1,4-benzodioxanyl, coumarin, dihydrocoumarin, 1,5-naphthyridinyl, benzofuryl (particularly 3-, 4-, 5-, 6- and 7-benzofuryl), 2,3-dihydrobenzofuryl, 1,2-benzisoxazolyl, benzothienyl (particularly 3-, 4-, 5-, 6-, and 7-benzothienyl), benzoxazolyl, benzothiazolyl (particularly 2-benzothiazolyl and 5-benzothiazolyl), purinyl, benzimidazolyl (particularly 2-benzimidazolyl), benztriazolyl, thioxanthinyl, carbazolyl, carbolinyl, acridinyl, pyrrolizidinyl, and quinolizidinyl. The aforementioned listing of heterocyclyl and heteroaryl moieties is intended to be representative and not limiting. As used herein, the term “amino aryl” refers to an aryl moiety which contains an amino moiety. Such amino moieties may include, but are not limited to primary amines, secondary amines, tertiary amines, masked amines, or protected amines. Such tertiary amines, masked amines, or protected amines may be converted to primary amine or secondary amine moieties. Additionally, the amine moiety may include an amine-like moiety which has similar chemical characteristics as amine moieties, including but not limited to chemical reactivity. As used herein, the term “substituted” means that an atom or group of atoms has replaced hydrogen as the substituent attached to another group. For aryl, aryl-(C1-C4)alkyl and heterocyclyl groups, the term “substituted” as applied to the rings of these groups refers to any level of substitution, namely mono-, di-, tri-, tetra-, or penta-substitution, where such substitution is permitted. The substituents are independently selected, and substitution may be at any chemically accessible position. In one embodiment, the substituents vary in number between one and four. In another embodiment, the substituents vary in number between one and three. In yet another embodiment, the substituents vary in number between one and two. In yet another embodiment, the substituents are independently selected from the group Attorney Docket No.046531-5034-00WO consisting of C1-6 alkyl, -OH, C1-6 alkoxy, halo, amino, acetamido and nitro. In yet another embodiment, the substituents are independently selected from the group consisting of C1-6alkyl, C1-6 alkoxy, halo, acetamido, and nitro. As used herein, where a substituent is an alkyl or alkoxy group, the carbon chain may be branched, straight or cyclic, with straight being preferred. As used herein, the term “optionally substituted” means that the referenced group may be substituted or unsubstituted. In one embodiment, the referenced group is optionally substituted with zero substituents, i.e., the referenced group is unsubstituted. In another embodiment, the referenced group is optionally substituted with one or more additional group(s) individually and independently selected from groups described herein. In one embodiment, the substituents are independently selected from the group consisting of oxo, halogen, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, alkyl (including straight chain, branched and / or unsaturated alkyl), substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, fluoro alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, fluoroalkoxy, -S-alkyl, S(=O)2alkyl, - C(=O)NH(substituted or unsubstituted alkyl, or substituted or unsubstituted phenyl), - C(=O)N(H or alkyl)2, -OC(=O)N(substituted or unsubstituted alkyl)2, -NHC(=O)NH(substituted or unsubstituted alkyl, or substituted or unsubstituted phenyl), -NHC(=O)alkyl, -N(substituted or unsubstituted alkyl)C(=O)(substituted or unsubstituted alkyl), -NHC(=O)(substituted or unsubstituted alkyl), -C(OH)(substituted or unsubstituted alkyl)2, and -C(NH2)(substituted or unsubstituted alkyl)2. In another embodiment, by way of example, an optional substituent is selected from oxo, fluorine, chlorine, bromine, iodine, -CN, -NH2, -OH, -NH(CH3), -N(CH3)2, -CH3, - CH2CH3, -CH(CH3)2, -CF3, -CH2CF3, -OCH3, -OCH2CH3, -OCH(CH3)2, -OCF3, - OCH2CF3, -S(=O)2-CH3, -C(=O)NH2, -C(=O)-NHCH3, -NHC(=O)NHCH3, -C(=O)CH3, - ON(O)2, and -C(=O)OH. In yet one embodiment, the substituents are independently selected from the group consisting of C1-6alkyl, -OH, C1-6alkoxy, halo, amino, acetamido, oxo and nitro. In yet another embodiment, the substituents are independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halo, acetamido, and nitro. As used herein, where a substituent is an alkyl or alkoxy group, the carbon chain may be branched, straight or cyclic. As used herein, the term “analog,” “analogue,” or “derivative” is meant to refer to a chemical compound or molecule made from a parent compound or molecule by one or more chemical reactions. As such, an analog can be a structure having a structure similar to that of the small molecule therapeutic agents described herein or can be based on a scaffold of a Attorney Docket No.046531-5034-00WO small molecule therapeutic agents described herein, but differing from it in respect to certain components or structural makeup, which may have a similar or opposite action metabolically. An analog or derivative can also be a small molecule that differs in structure from the reference molecule, but retains the essential properties of the reference molecule. An analog or derivative may change its interaction with certain other molecules relative to the reference molecule. An analog or derivative molecule may also include a salt, an adduct, tautomer, isomer, or other variant of the reference molecule. Ranges: throughout this disclosure, various aspects of the present invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Description The present invention is based, in part, on the unexpected discovery of cilagicin compounds as antibiotics which have activity against multidrug resistant pathogens. In one embodiment, the present invention provides compounds or a therapeutic compound comprising a desired activity. In one embodiment, the compound is an antibiotic. In one embodiment, the antibiotic compound of the present invention can be used in the treatment of bacterial infections. In one embodiment, the antibiotic compound of the present invention can be used in the treatment of gram positive bacterial infections. In certain embodiments, the use of the antibiotic compound of the present invention in the treatment of bacterial infections optionally includes a pharmaceutically acceptable carrier, excipient or adjuvant. In one embodiment, the compound can be biosynthesized via heterologous expression of a biosynthetic gene. Thus, in one aspect, the invention provides compounds and methods for synthesizing cilagicin compounds. In one embodiment, the invention provides a nucleic acid encoding cilagicin compounds. In one embodiment, the nucleic acid is an isolated nucleic acid. In one embodiment, the nucleic acid is transformed into a cell. Attorney Docket No.046531-5034-00WO Compounds In one aspect, the present invention provides a compound comprising the structure of Formula (I) or a an a a acceptable salt, or a derivative thereof. In one aspect of the present invention, the compound inhibits cell wall biosynthesis. In one aspect of the present invention, the compound specifically binds at least one undecaprenyl phosphorylate, undecaprenyl pyrophosphate, or a combination thereof. In one embodiment, the compound is a zwitterion. In some embodiments, the zwitterion comprises at least two positively charged residues and at least two negatively charged residues. In some embodiments, the compound comprises at least one amino acid sequence selected from at least one amino acid sequence as set forth in SEQ ID NO: 1-49, amino acid sequence from Figure 2A, at least one amino acid sequence selected from Figure 4A, at least one selected from Figure 6, or any combination thereof. In some embodiments, X is selected from O, S, N(R14), or any combination thereof. For example, in one embodiment, X is O. In some embodiments, each occurrence of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14is independently selected from hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, Attorney Docket No.046531-5034-00WO carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, or any combinations thereof. For example, in some embodiments, each occurrence of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14is independently selected from hydrogen, alkyl, alkenyl, aryl, aryl alkyl, aminoalkyl, hydroxyalkyl, or any combination thereof. In other embodiments, each occurrence of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14is independently selected from hydrogen, linear C1-C10 alkyl, branched C1-C10 alkyl, linear aryl-C1-C10 alkyl, branched aryl-C1-C10alkyl, linear amino-C1-C10alkyl, amino-branched C1-C10alkyl, linear hydroxy-C1-C10 alkyl, hydroxy-branched C1-C10 alkyl, linear C1-C10 alkenyl, branched C1-C10 alkenyl, linear aryl-C1-C10alkenyl, branched aryl-C1-C10alkenyl, linear amino-C1-C10alkenyl, amino-branched C1-C10 alkenyl, linear hydroxy-C1-C10 alkenyl, hydroxy-branched C1-C10alkenyl, or any combination thereof. In some embodiments, m is independently an integer from 0 to 100. For example, in one embodiment, m is an integer of 0. In one embodiment, m is an integer of 1. In one embodiment, m is an integer of 2. In one embodiment, m is an integer of 3. In one embodiment, m is an integer of 4. In one embodiment, m is an integer of 5. In one embodiment, m is an integer of 6. In one embodiment, m is an integer of 7. In one embodiment, m is an integer of 8. In one embodiment, m is an integer of 9. In one embodiment, m is an integer of 10. In one embodiment, m is an integer of 11. In one embodiment, m is an integer of 12. In one embodiment, m is an integer of 13. In one embodiment, m is an integer of 14. In one embodiment, m is an integer of 15. In one embodiment, m is an integer of 16. In one embodiment, m is an integer of 17. In one embodiment, m is an integer of 18. In one embodiment, m is an integer of 19. In one embodiment, m is an integer of 20. In one embodiment, m is an integer of 30. In one embodiment, m is an integer of 40. In one embodiment, m is an integer of 50. In one embodiment, m is an integer of 60. In one embodiment, m is an integer of 70. In one embodiment, m is an integer of 80. In one embodiment, m is an integer of 90. In one embodiment, m is an integer of 100. For example, in some embodiments, the compound of the present invention comprises a compound selected from the group consisting of: Attorney Docket No.046531-5034-00WO , or a racemate, an salt, or a derivative thereof; OH O O , or a racemate, an salt, or a derivative thereof; OH O , or a racemate, an salt, or a Attorney Docket No.046531-5034-00WO derivative thereof; , or a racemate, an salt, or a derivative thereof; and any combination thereof. In one embodiment, the compound comprises one of the following compounds, or any racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or derivative thereof: , , Attorney Docket No.046531-5034-00WO OH OH O H N HO O , In one embodiment, the compound is represented by Formula II, or any racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or derivative thereof: In some embodiments, the compound is represented by the below Formula (IIa), or any racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or derivative Attorney Docket No.046531-5034-00WO thereof: In some embodiments, R1, R2, R3, and R4are each independently selected from the group consisting of hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof. In some embodiments, L represents a group of the formula -C(O)(CH2)p-(Y)q-(CH2)r- H. In some embodiments, q and r independently represent an integer having a value between 1 and 20. In some embodiments, q represents 0 or 1. In some embodiments, Y represents cis or trans -C(H)=C(H)-. In one embodiment, L represents one of the following substituents: . In one embodiment, values: Attorney Docket No.046531-5034-00WO wherein Dab represents the non-canonic residue 2,4-diaminobutyric acid having the side change H2N–(CH2)2–. In one embodiment, the compound is represented by Formula III, or any racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or derivative thereof: OH O In one embodiment, the compound is represented by Formula IIIa, or any racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or derivative thereof:

[0004] Attorney Docket No.046531-5034-00WO In some group hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof. In one embodiment, R1comprises a group selected from the group consisting of biphenyl, pyrene, styrene, indole, naphthalene, cyclopropane, phenyl, pyrrolidine, indene, indane, C5-C20alkyl, C5-C20alkyl-ene, and C5-C20alkyl-diene. In one embodiment, R1represents one of the following groups:

[0005] Attorney Docket No.046531-5034-00WO n or or one m 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. In one embodiment, R1represents one of the following groups: The and such salts are included in the present invention. The term “salts” embraces addition salts of free acids or free bases that are compounds of the present invention. In one aspect, the present invention relates, in part, to compositions comprising one or more compounds of the present invention. In some embodiments, the composition comprises one or more compounds comprising the structure of Formula (I), or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof. In some embodiments, the composition is the pharmaceutical composition. In another aspect, the present invention relates, in part, to nucleic acid molecules encoding one or more compounds of the present invention. In some embodiments, the nucleic acid molecules encoding one or more compounds comprising the structure of Formula (I), or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof. In another aspect, the present invention relates, in part, to compositions comprising one or more nucleic acid molecules of the present invention. In some embodiments, the Attorney Docket No.046531-5034-00WO composition comprises one or more nucleic acid molecules encoding one or more compounds comprising the structure of Formula (I), or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof. In some embodiments, the composition is the pharmaceutical composition. In another aspect, the present invention relates, in part, to genetically engineered cells producing one or more compounds of the present invention. In some embodiments, the genetically engineered cells producing one or more compounds comprising the structure of Formula (I), or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof. In another aspect, the present invention relates, in part, to compositions comprising one or more genetically engineered cells of the present invention. In some embodiments, the composition comprises one or more genetically engineered cells producing one or more compounds comprising the structure of Formula (I), or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof. In some embodiments, the composition is the pharmaceutical composition. Methods of Generating Compounds In one aspect, the present invention relates, in part, to a method of generating one or more compounds of the present invention. In various embodiments, the compounds of the present invention can be generated using any method known to those of skill in the art. For example, in one embodiment, the compounds can be synthesized using any method known to those of skill in the art. For example, the compounds of the present invention may be synthesized using techniques well-known in the art of organic synthesis. The starting materials and intermediates required for the synthesis may be obtained from commercial sources or synthesized according to methods known to those skilled in the art. In one embodiment, the present invention provides methods of generating the compounds of the present invention via isolated nucleic acids encoding the compound of the present invention. In one embodiment, when the nucleic acids are administered to a subject, they produce the compound of the present invention. In one embodiment, when the nucleic acids are administered to a subject, they produce an antibacterial effect. In another embodiment, the present invention provides methods of generating the compounds of the present invention via isolated nucleic acids and vectors encoding the compound of the present invention. In one embodiment, when the nucleic acids and vectors are administered to a subject, they produce the compound of the present invention. In one Attorney Docket No.046531-5034-00WO embodiment, when the nucleic acids and vectors are administered to a subject, they produce an antibacterial effect. The nucleic acid sequences include both the DNA sequence that is transcribed into RNA and the RNA sequence that is translated into a polypeptide. According to other embodiments, the polynucleotides of the present invention are inferred from the amino acid sequence of the polypeptides of the present invention. As is known in the art several alternative polynucleotides are possible due to redundant codons, while retaining the biological activity of the translated polypeptides. It is to be understood explicitly that the scope of the present invention encompasses homologs, analogs, variants, fragments, derivatives and salts, including shorter and longer polynucleotides as well as polynucleotide analogs with one or more nucleic acid substitution, as well as nucleic acid derivatives, non-natural nucleic acids and synthetic nucleic acids as are known in the art, with the stipulation that these modifications must preserve the activity of the original molecule. The invention should be construed to include any and all isolated nucleic acids which are homologous to the nucleic acids described and referenced herein. The skilled artisan would understand that the nucleic acids of the present invention encompass a RNA or a DNA sequence comprising a sequence of the present invention, and any modified forms thereof, including chemical modifications of the DNA or RNA which render the nucleotide sequence more stable when it is cell free or when it is associated with a cell. Chemical modifications of nucleotides may also be used to enhance the efficiency with which a nucleotide sequence is taken up by a cell or the efficiency with which it is expressed in a cell. Any and all combinations of modifications of the nucleotide sequences are contemplated in the present invention. The coding sequence may comprise a codon that may allow more efficient transcription of the coding sequence in the host cell. In one embodiment, viral vectors are provided herein which are capable of delivering a nucleic acid of the present invention to a cell. The expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Sambrook et al. (2001), and in Ausubel et al. (1997), and in other virology and molecular biology manuals. Viruses, which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers. (See, e.g., WO 01 / 96584; WO 01 / 29058; and U.S. Pat. No.6,326,193. Viral vectors, and Attorney Docket No.046531-5034-00WO especially retroviral vectors, have become the most widely used method for inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus I, adenoviruses and adeno-associated viruses, and the like. See, for example, U.S. Pat. Nos.5,350,674 and 5,585,362. Suitable host organisms include microorganisms, plant cells, and plants. The microorganism can be any microorganism suitable for expression of heterologous nucleic acids. In one embodiment the host organism of the present invention is a eukaryotic cell. In another embodiment the host organism is a prokaryotic cell. In one embodiment, the host organism is a fungal cell such as a yeast or filamentous fungus. In one embodiment the host organism may be a yeast cell. The host organism may also be a plant. plant or plant cell can be transformed by having a heterologous nucleic acid integrated into its genome, i.e., it can be stably transformed. Stably transformed cells typically retain the introduced nucleic acid with each cell division. A plant or plant cell can also be transiently transformed such that the recombinant gene is not integrated into its genome. Transiently transformed cells typically lose all or some portion of the introduced nucleic acid with each cell division such that the introduced nucleic acid cannot be detected in daughter cells after a certain number of cell divisions. In one embodiment, the engineered cell produces a compound comprising the structure of Formula (I). In one embodiment, the cell is a eukaryotic cell. In one embodiment, the cell may be a human cell, a non-human mammalian cell, a non-mammalian vertebrate cell, an invertebrate cell, an insect cell, a plant cell, a yeast cell, or a single cell eukaryotic organism. In one embodiment, the cell may be an adult cell or an embryonic cell (e.g., an embryo). In one embodiment, the cell may be a stem cell. Suitable stem cells include without limit embryonic stem cells, ES-like stem cells, fetal stem cells, adult stem cells, pluripotent stem cells, induced pluripotent stem cells, multipotent stem cells, oligopotent stem cells, unipotent stem cells and others. In one embodiment, the cell is a cell line cell. Non-limiting examples of suitable mammalian cells include Chinese hamster ovary (CHO) cells, baby hamster kidney (BHK) cells; mouse myeloma NS0 cells, mouse embryonic fibroblast 3T3 cells (NIH3T3), mouse B lymphoma A20 cells; mouse melanoma B16 cells; mouse myoblast C2C12 cells; mouse myeloma SP2 / 0 cells; mouse embryonic mesenchymal C3H-10T1 / 2 cells; mouse carcinoma CT26 cells, mouse prostate DuCuP cells; mouse breast EMT6 cells; mouse hepatoma Attorney Docket No.046531-5034-00WO Hepa1c1c7 cells; mouse myeloma J5582 cells; mouse epithelial MTD-1A cells; mouse myocardial MyEnd cells; mouse renal RenCa cells; mouse pancreatic RIN-5F cells; mouse melanoma X64 cells; mouse lymphoma YAC-1 cells; rat glioblastoma 9L cells; rat B lymphoma RBL cells; rat neuroblastoma B35 cells; rat hepatoma cells (HTC); buffalo rat liver BRL 3A cells; canine kidney cells (MDCK); canine mammary (CMT) cells; rat osteosarcoma D17 cells; rat monocyte / macrophage DH82 cells; monkey kidney SV-40 transformed fibroblast (COS7) cells; monkey kidney CVI-76 cells; African green monkey kidney (VERO-76) cells; human embryonic kidney cells (HEK293, HEK293T); human cervical carcinoma cells (HELA); human lung cells (W138); human liver cells (Hep G2); human U2-OS osteosarcoma cells, human A549 cells, human A-431 cells, human SW48 cells, human HCT116 cells, and human K562 cells. An extensive list of mammalian cell lines may be found in the American Type Culture Collection catalog (ATCC, Manassas, Va.). In one embodiment, the cell can be a prokaryotic cell or a eukaryotic cell. In one embodiment, the cell is a prokaryotic cell. In one embodiment, the cell is a genetically engineered bacteria cell. In one embodiment, the genetically engineered bacteria cell is a non-pathogenic bacteria cell. In some embodiments, the genetically engineered bacteria cell is a commensal bacteria cell. In some embodiments, the genetically engineered bacteria cell is a probiotic bacteria cell. In some embodiments, the genetically engineered bacteria cell is a naturally pathogenic bacteria cell that is modified or mutated to reduce or eliminate pathogenicity. Exemplary bacteria include, but are not limited to Acinetobacter baumannii, Bacillus, Bacteroides, Bifidobacterium, Brevibacteria, Clostridium, Enterococcus, Escherichia coli, Lactobacillus, Lactococcus, Saccharomyces, and Staphylococcus, e.g., Bacillus coagulans, Bacillus subtilis, Bacteroides fragilis, Bacteroides subtilis, Bacteroides thetaiotaomicron, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Clostridium butyricum, Clostridium difficile, Enterobacter species, Enterobacter cloacae, Enterococcus casseliflavus, Enterococcus faecium, Enterococcus gallinarum, Escherichia coli, Klebsiella pneumoniae, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactococcus lactis, Pseudomonas aeruginosa, Saccharomyces boulardii, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyrogens. In some embodiments, the genetically engineered bacteria are Escherichia coli strain Nissle 1917 (E. coli Nissle), a Gram-negative bacterium of the Enterobacteriaceae family that Attorney Docket No.046531-5034-00WO “has evolved into one of the best characterized probiotics” (Ukena et al., 2007). The strain is characterized by its complete harmlessness (Schultz, 2008), and has GRAS (generally recognized as safe) status (Reister et al., 2014, emphasis added). Genomic sequencing confirmed that E. coli Nissle lacks prominent virulence factors (e.g., E. coli α-hemolysin, P- fimbrial adhesins) (Schultz, 2008). In addition, it has been shown that E. coli Nissle does not carry pathogenic adhesion factors, does not produce any enterotoxins or cytotoxins, is not invasive, and not uropathogenic (Sonnenborn et al., 2009). As early as in 1917, E. coli Nissle was packaged into medicinal capsules, called Mutaflor, for therapeutic use. E. coli Nissle has since been used to treat ulcerative colitis in humans in vivo (Rembacken et al., 1999), to treat inflammatory bowel disease, Crohn’s disease, and pouchitis in humans in vivo (Schultz, 2008), and to inhibit enteroinvasive Salmonella, Legionella, Yersinia, and Shigella in vitro (Altenhoefer et al., 2004). It is commonly accepted that E. coli Nissle’s therapeutic efficacy and safety have convincingly been proven (Ukena et al., 2007). One of ordinary skill in the art would appreciate that the genetic modifications disclosed herein may be modified and adapted for other species, strains, and subtypes of bacteria. Treatment and Prevention Methods In one aspect, the invention provides methods of treating or preventing an infection in a subject in need thereof. In some embodiments, the method comprises administering to the subject at least one compound of the present invention (e.g., at least one compound comprising the structure of Formula (I)), at least one nucleic acid molecule of the present invention (e.g., at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I)), at least one genetically engineered cell of the present invention (e.g., at least one genetically engineered cell producing a compound comprising the structure of Formula (I)), at least one composition of the present invention (e.g., at least one composition comprising at least one compound comprising the structure of Formula (I), at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I), at least one genetically engineered cell producing a compound comprising the structure of Formula (I), or any combination), or any combination thereof. For example, in some embodiments, the method comprises administering to the subject an effective amount of a composition comprising at least one compound of the present invention (e.g., at least one compound of Formula (I)). Attorney Docket No.046531-5034-00WO In some embodiments, the method comprises administering to the subject an effective amount of a composition comprising at least one nucleic acid of the present invention (e.g., at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I)). In some embodiments, the method comprises administering to the subject an effective amount of a composition comprising at least one genetically engineered cell of the present invention (e.g., at least one genetically engineered cell producing a compound comprising the structure of Formula (I)). In some embodiments, the method comprises administering to the subject an effective amount of a composition comprising at least one compound of the present invention (e.g., at least one compound of Formula (I)). In some embodiments, the method comprises administering to the subject an effective amount of a composition comprising at least one nucleic acid of the present invention. In some embodiments, the method comprises administering to the subject an effective amount of a composition comprising at least one genetically engineered cell of the present invention. In another aspect, the present invention provides methods of administering an effective amount of at least one compound of the present invention (e.g., at least one compound comprising the structure of Formula (I)), at least one nucleic acid molecule of the present invention (e.g., at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I)), at least one genetically engineered cell of the present invention (e.g., at least one genetically engineered cell producing a compound comprising the structure of Formula (I)), at least one composition of the present invention (e.g., at least one composition comprising at least one compound comprising the structure of Formula (I), at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I), at least one genetically engineered cell producing a compound comprising the structure of Formula (I), or any combination), or any combination thereof to a subject. In some embodiments, the subject has an infection. In some embodiments, the subject is exposed to or infected with a pathogen. In some embodiments, the method treats or prevents a pathogen infection. In some embodiments, the pathogen is selected from any pathogen listed in Figure 6, Table 1, Table 6, or any combination thereof. In some embodiments, the method treats or prevents a bacterial infection. In one embodiment, the method treats or prevents a gram-positive bacterial infection. In one Attorney Docket No.046531-5034-00WO embodiment, the bacterial infection is resistant to antibiotics. For example, in one embodiment, the bacterial infection is resistant to one or more of, beta-lactams, including methicillin, oxacillin, or penicillin, tetracyclines, gentamicin, kanamycin, erythromycin, spectinomycin, and vancomycin. Exemplary bacterial infections that may be treated by way of the present invention includes, but is not limited to, infections caused by bacteria from the taxonomic genus of Acinetobacter, Bacillus, Bartonella, Bordetella, Borrelia, Brucella, Campylobacter, Chlamydia, Chlamydophila, Clostridium, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Francisella, Haemophilus, Helicobacter, Klebsiella, Legionella, Leptospira, Listeria, Mycobacterium, Mycoplasma, Neisseria, Pseudomonas, Rickettsia, Salmonella, Shigella, Staphylococcus, Streptococcus, Treponema, Ureaplasma, Vibrio, and Yersinia. In some embodiments, the bacterial infection is an infection of Acinetobacter baumannii, Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bartonella henselae, Bartonella quintana, Bordetella pertussis, Borrelia burgdorferi, Borrelia garinii, Borrelia afzelii, Borrelia recurrentis, Brucella abortus, Brucella canis, Brucella melitensis, Brucella suis, Campylobacter jejuni, Chlamydia pneumoniae, Chlamydia trachomatis, Chlamydophila psittaci, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheriae, Enterococcus casseliflavus, Enterobacter cloacae, Enterococcus faecalis, Enterococcus faecium, Enterococcus gallinarum, Escherichia coli, Francisella tularensis, Haemophilus influenzae, Helicobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Leptospira santarosai, Leptospira weilii, Leptospira noguchii, Listeria monocytogenes, Morexella species, Moraxella osloensis, Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus species, Proteus vulgaris, Pseudomonas aeruginosa, Rickettsia rickettsii, Salmonella typhi, Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Treponema pallidum, Ureaplasma urealyticum, Vibrio cholerae, Yersinia pestis, Yersinia enterocolitica, or Yersinia pseudotuberculosis. In one embodiment, the bacterial infection is a Listeria monocytogenes infection. In one embodiment, the bacterial infection is an infection of S. aureus USA300, S. aureus COL, S. aureus BAA-42, S. aureus NRS100, S. aureus NRS108, S. aureus NRS140, S. aureus NRS146, E. faecium VRE, E. faecium Com15, S. pneumoniae, S. mutans, B. subtilis, L. rhamnosus, E. coli, C. albicans, or C. neoformans. Attorney Docket No.046531-5034-00WO Exemplary diseases caused by bacterial infections which may be treated using compositions of the present invention, include but are not limited to, bacterially mediated meningitis, sinus tract infections, pneumonia, endocarditis, pancreatitis, appendicitis, gastroenteritis, biliary tract infections, soft tissue infections, urinary tract infections, cystitis, pyelonephritis, osteomyelitis, bacteremia, Actinomycosis, Whooping cough, Secondary bacterial pneumonia, Lyme disease (B. burgdorferi), Relapsing fever, Brucellosis, Enteritis, bloody diarrhea, Guillain–Barré syndrome, Atypical pneumonia, Trachoma, Neonatal conjunctivitis, Neonatal pneumonia, Nongonococcal urethritis(NGU), Urethritis, Pelvic inflammatory disease, Epididymitis, Prostatitis, Lymphogranuloma venereum (LGV), Psittacosis, Botulism: Mainly muscle weakness and paralysis, Pseudomembranous colitis, Anaerobic cellulitis, Gas gangrene Acutefood poisoning, Tetanus, and Diphtheria. However, the invention should not be limited to only treating bacterial infection. The invention encompasses compounds having an antimicrobial activity including but not limited to antibacterial, antimycobacterial, antifungal, antiviral and the likes. In one aspect, the invention provides methods of killing a bacterial cell or inhibiting the grown of a bacterial cell. In some embodiments, the method comprises administering to the cell at least one compound of the present invention (e.g., at least one compound comprising the structure of Formula (I)), at least one nucleic acid molecule of the present invention (e.g., at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I)), at least one genetically engineered cell of the present invention (e.g., at least one genetically engineered cell producing a compound comprising the structure of Formula (I)), at least one composition of the present invention (e.g., at least one composition comprising at least one compound comprising the structure of Formula (I), at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I), at least one genetically engineered cell producing a compound comprising the structure of Formula (I), or any combination), or any combination thereof. In some embodiments, the method comprises administering to the cell an effective amount of a composition comprising at least one compound of the present invention. In some embodiments, the method comprises administering to the cell an effective amount of a composition comprising at least one nucleic acid of the present invention. In one embodiment the bacterial cell is a gram positive bacterial cell. In one embodiment, the bacterial cell is resistant to antibiotics. For example, in one embodiment, the bacterial cell is resistant to one or more of, beta-lactams, including methicillin, oxacillin, or penicillin, tetracyclines, gentamicin, kanamycin, erythromycin, spectinomycin, and vancomycin. Attorney Docket No.046531-5034-00WO In another aspect, the invention provides compositions and methods for treating and / or preventing a disease or disorder related to the detrimental growth and / or proliferation of a bacterial cell in vivo, ex vivo or in vitro. In some embodiments, the method comprises administering at least one compound of the present invention (e.g., at least one compound comprising the structure of Formula (I)), at least one nucleic acid molecule of the present invention (e.g., at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I)), at least one genetically engineered cell of the present invention (e.g., at least one genetically engineered cell producing a compound comprising the structure of Formula (I)), at least one composition of the present invention (e.g., at least one composition comprising at least one compound comprising the structure of Formula (I), at least one isolated nucleic acid molecule encoding a compound comprising the structure of Formula (I), at least one genetically engineered cell producing a compound comprising the structure of Formula (I), or any combination), or any combination thereof. In certain embodiments, the method comprises administering a composition comprising an effective amount of a composition provided by the present invention to a subject, wherein the composition is effective in inhibiting or preventing the growth and / or proliferation of a bacterial cell. In certain embodiments, the bacterial cell is a Gram-positive bacterial cell, e.g., a bacteria of a genera such as Staphylococcus, Streptococcus, Enterococcus, (which are cocci) and Bacillus, Corynebacterium, Nocardia, Clostridium, Actinobacteria, and Listeria (which are rods and can be remembered by the mnemonic obconical), Mollicutes, bacteria-like Mycoplasma, Actinobacteria. In certain embodiments, the bacterial cell is a Gram- bacteria cell, e.g., a bacteria of a genera such as Acinetobacter, Citrobacter, Enterobacter, Enterococcus, Escherichia, Helicobacter, Hemophilus, Klebsiella, Legionella, Moraxella, Neisseria, Proteus, Pseudomonas, Salmonella, Staphylococcus, and Yersinia. The compounds as described herein and compositions comprising them may thus be for use in the treatment of bacterial infections by the above-mentioned Gram+ or Gram- bacteria. In one embodiment, the method further comprises administering a second therapeutic agent. In one embodiment, the second therapeutic agent is an antibiotic agent. In one embodiment, the compound of the present invention and the at least one additional antibiotic agent act synergistically in preventing, reducing or disrupting microbial growth. Non-limiting examples of the at least one additional antibiotic agents include levofloxacin, doxycycline, neomycin, clindamycin, minocycline, gentamycin, rifampin, chlorhexidine, chloroxylenol, methylisothizolone, thymol, α-terpineol, cetylpyridinium Attorney Docket No.046531-5034-00WO chloride, hexachlorophene, triclosan, nitrofurantoin, erythromycin, nafcillin, cefazolin, imipenem, astreonam, gentamicin, sulfamethoxazole, vancomycin, ciprofloxacin, trimethoprim, rifampin, metronidazole, clindamycin, teicoplanin, mupirocin, azithromycin, clarithromycin, ofoxacin, lomefloxacin, norfloxacin, nalidixic acid, sparfloxacin, pefloxacin, amifloxacin, gatifloxacin, moxifloxacin, gemifloxacin, enoxacin, fleroxacin, minocycline, linexolid, temafloxacin, tosufloxacin, clinafloxacin, sulbactam, clavulanic acid, amphotericin B, fluconazole, itraconazole, ketoconazole, nystatin, penicillins, cephalosporins, carbepenems, beta-lactams antibiotics, aminoglycosides, macrolides, lincosamides, glycopeptides, tetracylines, chloramphenicol, quinolones, fucidines, sulfonamides, trimethoprims, rifamycins, oxalines, streptogramins, lipopeptides, ketolides, polyenes, azoles, echinocandines, and any combination thereof. In one embodiment, the compositions of the present invention find use in removing at least a portion of or reducing the number of microorganisms and / or biofilm-embedded microorganisms attached to the surface of a medical device or the surface of a subject’s body (such as the skin of the subject, or a mucous membrane of the subject, such as the vagina, anus, throat, eyes or ears). In one embodiment, the compositions of the present invention find further use in coating the surface of a medical device, thus inhibiting or disrupting microbial growth and / or inhibiting or disrupting the formation of biofilm on the surface of the medical device. The compositions of the present invention find further use in preventing or reducing the growth or proliferation of microorganisms and / or biofilm-embedded microorganisms on the surface of a medical device or on the surface of a subject’s body. However, the invention is not limited to applications in the medical field. Rather, the invention includes using a compound or an analog thereof as an antimicrobial and / or antibiofilm agent in any setting. The composition of the present invention may be administered to a patient or subject in need in a wide variety of ways, including by aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation. The compositions described herein may be administered to a patient subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous (i.v.) injection, or intraperitoneally. In one embodiment, the composition is administered systemically to the subject. In one embodiment, the compositions of the present invention are administered to a patient by i.v. injection. In one embodiment, the composition is administered locally to the subject. In one embodiment, the compositions of the present invention are administered to a patient topically. Any administration may be a single application of a composition of invention or multiple applications. Administrations may be to single site or to more than one site in the individual Attorney Docket No.046531-5034-00WO to be treated. Multiple administrations may occur essentially at the same time or separated in time. In one aspect, the compositions of the present invention may be in the form of a coating that is applied to the surface of a medical device or the surface of a subject’s body. In one embodiment, the coating prevents or hinders microorganisms and / or biofilm-embedded microorganisms from growing and proliferating on at least one surface of the medical device or at least one surface of the subject’s body. In another embodiment, the coating facilitates access of antimicrobial agents to the microorganisms and / or biofilm-embedded microorganisms, thus helping prevent or hinder the microorganisms and / or biofilm-embedded microorganisms from growing or proliferating on at least one surface of the medical device or at least one surface of the subject’s body. The compositions of the present invention may also be in the form of a liquid or solution, used to clean the surface of medical device or the surface of a subject’s body, on which microorganisms and / or biofilm-embedded microorganisms live and proliferate. Such cleaning of the medical device or body surface may occur by flushing, rinsing, soaking, or any additional cleaning method known to those skilled in the art, thus removing at least a portion of or reducing the number of microorganisms and / or biofilm-embedded microorganisms attached to at least one surface of the medical device or at least one surface of the subject’s body. Subjects to which administration of the pharmaceutical compositions of the present invention is contemplated include, but are not limited to, humans and other primates, mammals including but not limited to non-human mammals such as non-human primates, cattle, pigs, horses, sheep, cats, and dogs. Pharmaceutical compositions of the present invention may be administered in a manner appropriate to the disease to be treated (or prevented). The quantity and frequency of administration will be determined by such factors as the condition of the subject, and the type and severity of the subject’s disease, although appropriate dosages may be determined by clinical trials. When “therapeutic amount” is indicated, the precise amount of the compositions of the present invention to be administered can be determined by a physician with consideration of individual differences in age, weight, disease type, extent of disease, and condition of the patient (subject). Dosage and Formulation (Pharmaceutical compositions) The invention also encompasses the use of pharmaceutical compositions comprising a Attorney Docket No.046531-5034-00WO compound of the present invention, a nucleic acid of the present invention, or salts thereof. Such a pharmaceutical composition may comprise of at least one a compound of the present invention, a nucleic acid of the present invention, or salts thereof in a form suitable for administration to a subject, or the pharmaceutical composition may comprise at least one a compound of the present invention, a nucleic acid of the present invention, or salts thereof, and one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these. The compound or nucleic acid of the present invention may be present in the pharmaceutical composition in the form of a physiologically acceptable salt, such as in combination with a physiologically acceptable cation or anion, as is well known in the art. Administration of the therapeutic agent in accordance with the present invention may be continuous or intermittent, depending, for example, upon the recipient’s physiological condition, whether the purpose of the administration is therapeutic or prophylactic, and other factors known to skilled practitioners. The administration of the agents of the present invention may be essentially continuous over a preselected period of time or may be in a series of spaced doses. Both local and systemic administration is contemplated. The amount administered will vary depending on various factors including, but not limited to, the composition chosen, the particular disease, the weight, the physical condition, and the age of the subject, and whether prevention or treatment is to be achieved. Such factors can be readily determined by the clinician employing animal models or other test systems which are well known to the art The formulations may, where appropriate, be conveniently presented in discrete unit dosage forms and may be prepared by any of the methods well known to pharmacy. Such methods may include the step of bringing into association the therapeutic agent with liquid carriers, solid matrices, semi-solid carriers, finely divided solid carriers or combinations thereof, and then, if necessary, introducing or shaping the product into the desired delivery system. In one embodiment, the pharmaceutical compositions useful for practicing the methods of the present invention may be administered to deliver a dose of between 1 ng / kg / day and 100 mg / kg / day. In another embodiment, the pharmaceutical compositions useful for practicing the invention may be administered to deliver a dose of between 1 ng / kg / day and 500 mg / kg / day. Typically, dosages which may be administered in a method of the present invention to a mammal, preferably a human, range in amount from 0.5 μg to about 50 mg per kilogram of Attorney Docket No.046531-5034-00WO body weight of the mammal, while the precise dosage administered will vary depending upon any number of factors, including but not limited to, the type of mammal and type of disease state being treated, the age of the mammal and the route of administration. Preferably, the dosage of the compound will vary from about 1 μg to about 10 mg per kilogram of body weight of the mammal. More preferably, the dosage will vary from about 3 μg to about 5 mg per kilogram of body weight of the mammal. The relative amounts of the active ingredient, the pharmaceutically acceptable carrier, and any additional ingredients in a pharmaceutical composition of the present invention will vary, depending upon the identity, size, and condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w / w) active ingredient. The composition may be administered to a mammal as frequently as several times daily, or it may be administered less frequently, such as once a day, once a week, once every two weeks, once a month, or even less frequently, such as once every several months or even once a year or less. The frequency of the dose will be readily apparent to the skilled artisan and will depend upon any number of factors, such as, but not limited to, the type and severity of the disease being treated, the type and age of the mammal, etc. When the therapeutic agents of the present invention are prepared for administration, they are preferably combined with a pharmaceutically acceptable carrier, diluent or excipient to form a pharmaceutical formulation, or unit dosage form. The total active ingredients in such formulations include from 0.1 to 99.9% by weight of the formulation. A “pharmaceutically acceptable” is a carrier, diluent, excipient, and / or salt that is compatible with the other ingredients of the formulation, and not deleterious to the recipient thereof. The active ingredient for administration may be present as a powder or as granules; as a solution, a suspension or an emulsion. Pharmaceutical formulations containing the therapeutic agents of the present invention can be prepared by procedures known in the art using well known and readily available ingredients. The therapeutic agents of the present invention can also be formulated as solutions appropriate for parenteral administration, for instance by intramuscular, subcutaneous or intravenous routes. The pharmaceutical formulations of the therapeutic agents of the present invention can also take the form of an aqueous or anhydrous solution or dispersion, or alternatively the form of an emulsion or suspension. Thus, the therapeutic agent may be formulated for parenteral administration (e.g., by Attorney Docket No.046531-5034-00WO injection, for example, bolus injection or continuous infusion) and may be presented in unit dose form in ampules, pre-filled syringes, small volume infusion containers or in multi-dose containers with an added preservative. The active ingredients may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Alternatively, the active ingredients may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g., sterile, pyrogen- free water, before use. It will be appreciated that the unit content of active ingredient or ingredients contained in an individual aerosol dose of each dosage form need not in itself constitute an effective amount for treating the particular indication or disease since the necessary effective amount can be reached by administration of a plurality of dosage units. Moreover, the effective amount may be achieved using less than the dose in the dosage form, either individually, or in a series of administrations. The pharmaceutical formulations of the present invention may include, as optional ingredients, pharmaceutically acceptable carriers, diluents, solubilizing or emulsifying agents, and salts of the type that are well-known in the art. Specific non-limiting examples of the carriers and / or diluents that are useful in the pharmaceutical formulations of the present invention include water and physiologically acceptable buffered saline solutions, such as phosphate buffered saline solutions pH 7.0-8.0. The compounds and polypeptides (active ingredients) of this invention can be formulated and administered to treat a variety of disease states by any means that produces contact of the active ingredient with the agent’s site of action in the body of the organism. They can be administered by any conventional means available for use in conjunction with pharmaceuticals, either as individual therapeutic active ingredients or in a combination of therapeutic active ingredients. They can be administered alone, but are generally administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice. In general, water, suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration contain the active ingredient, suitable stabilizing agents and, if necessary, buffer substances. Antioxidizing agents such as sodium bisulfate, sodium sulfite or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium Attorney Docket No.046531-5034-00WO Ethylenediaminetetraacetic acid (EDTA). In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. Suitable pharmaceutical carriers are described in Remington’s Pharmaceutical Sciences, a standard reference text in this field. The active ingredients of the present invention may be formulated to be suspended in a pharmaceutically acceptable composition suitable for use in mammals and in particular, in humans. Such formulations include the use of adjuvants such as muramyl dipeptide derivatives (MDP) or analogs that are described in U.S. Patent Nos.4,082,735; 4,082,736; 4,101,536; 4,185,089; 4,235,771; and 4,406,890. Other adjuvants, which are useful, include alum (Pierce Chemical Co.), lipid A, trehalose dimycolate and dimethyldioctadecylammonium bromide (DDA), Freund’s adjuvant, and IL-12. Other components may include a polyoxypropylene-polyoxyethylene block polymer (Pluronic®), a non-ionic surfactant, and a metabolizable oil such as squalene (U.S. Patent No.4,606,918). Additionally, standard pharmaceutical methods can be employed to control the duration of action. These are well known in the art and include control release preparations and can include appropriate macromolecules, for example polymers, polyesters, polyamino acids, polyvinyl, pyrolidone, ethylenevinylacetate, methyl cellulose, carboxymethyl cellulose or protamine sulfate. The concentration of macromolecules as well as the methods of incorporation can be adjusted in order to control release. Additionally, the agent can be incorporated into particles of polymeric materials such as polyesters, polyamino acids, hydrogels, poly (lactic acid) or ethylenevinylacetate copolymers. In addition to being incorporated, these agents can also be used to trap the compound in microcapsules. Accordingly, the pharmaceutical composition of the present invention may be delivered via various routes and to various sites in a mammal body to achieve a particular effect (see, e.g., Rosenfeld et al., 1991; Rosenfeld et al., 1991a; Jaffe et al., supra; Berkner, supra). One skilled in the art will recognize that although more than one route can be used for administration, a particular route can provide a more immediate and more effective reaction than another route. Local or systemic delivery can be accomplished by administration comprising application or instillation of the formulation into body cavities, inhalation or insufflation of an aerosol, or by parenteral introduction, comprising intramuscular, intravenous, peritoneal, subcutaneous, intradermal, as well as topical administration. The active ingredients of the present invention can be provided in unit dosage form wherein each dosage unit, e.g., a teaspoonful, tablet, solution, or suppository, contains a predetermined amount of the composition, alone or in appropriate combination with other Attorney Docket No.046531-5034-00WO active agents. The term “unit dosage form” as used herein refers to physically discrete units suitable as unitary dosages for human and mammal subjects, each unit containing a predetermined quantity of the compositions of the present invention, alone or in combination with other active agents, calculated in an amount sufficient to produce the desired effect, in association with a pharmaceutically acceptable diluent, carrier, or vehicle, where appropriate. The specifications for the unit dosage forms of the present invention depend on the particular effect to be achieved and the particular pharmacodynamics associated with the pharmaceutical composition in the particular host. In one embodiment, the compositions of the present invention are formulated using one or more pharmaceutically acceptable excipients or carriers. In one embodiment, the pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound or conjugate of the present invention and a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers that are useful, include, but are not limited to, glycerol, water, saline, ethanol and other pharmaceutically acceptable salt solutions such as phosphates and salts of organic acids. Examples of these and other pharmaceutically acceptable carriers are described in Remington’s Pharmaceutical Sciences (1991, Mack Publication Co., New Jersey). The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity may be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms may be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, sodium chloride, or polyalcohols such as mannitol and sorbitol, in the composition. Prolonged absorption of the injectable compositions may be brought about by including in the composition an agent that delays absorption, for example, aluminum monostearate or gelatin. In one embodiment, the pharmaceutically acceptable carrier is not DMSO alone. The present invention also provides pharmaceutical compositions comprising one or more of the compositions described herein. Formulations may be employed in admixtures with conventional excipients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for administration to subject. The pharmaceutical compositions may be sterilized and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, Attorney Docket No.046531-5034-00WO stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure buffers, coloring, and / or aromatic substances and the like. They may also be combined where desired with other active agents, e.g., other analgesic agents. As used herein, “additional ingredients” include, but are not limited to, one or more of the following: excipients; surface active agents; dispersing agents; inert diluents; granulating and disintegrating agents; binding agents; lubricating agents; coloring agents; preservatives; physiologically degradable compositions such as gelatin; aqueous vehicles and solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying agents, demulcents; buffers; salts; thickening agents; fillers; emulsifying agents; antioxidants; antibiotics; antifungal agents; stabilizing agents; and pharmaceutically acceptable polymeric or hydrophobic materials. Other “additional ingredients” that may be included in the pharmaceutical compositions of the present invention are known in the art and described, for example in Genaro, ed. (1985, Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, PA), which is incorporated herein by reference. The composition of the present invention may comprise a preservative from about 0.005% to 2.0% by total weight of the composition. The preservative is used to prevent spoilage in the case of exposure to contaminants in the environment. Examples of preservatives useful in accordance with the invention included but are not limited to those selected from the group consisting of benzyl alcohol, sorbic acid, parabens, imidurea and combinations thereof. A particularly preferred preservative is a combination of about 0.5% to 2.0% benzyl alcohol and 0.05% to 0.5% sorbic acid. In an embodiment, the composition includes an anti-oxidant and a chelating agent that inhibits the degradation of one or more components of the composition. Preferred antioxidants for some compounds are BHT, BHA, alpha-tocopherol and ascorbic acid in the preferred range of about 0.01% to 0.3% and more preferably BHT in the range of 0.03% to 0.1% by weight by total weight of the composition. Preferably, the chelating agent is present in an amount of from 0.01% to 0.5% by weight by total weight of the composition. Particularly preferred chelating agents include edetate salts (e.g. disodium edetate) and citric acid in the weight range of about 0.01% to 0.20% and more preferably in the range of 0.02% to 0.10% by weight by total weight of the composition. The chelating agent is useful for chelating metal ions in the composition that may be detrimental to the shelf life of the formulation. While BHT and disodium edetate are the particularly preferred antioxidant and chelating agent respectively for some compounds, other suitable and equivalent antioxidants and chelating agents may be substituted therefore as would be known to those skilled in the Attorney Docket No.046531-5034-00WO art. Liquid suspensions may be prepared using conventional methods to achieve suspension of the HMW-HA or other composition of the present invention in an aqueous or oily vehicle. Aqueous vehicles include, for example, water, and isotonic saline. Oily vehicles include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Liquid suspensions may further comprise one or more additional ingredients including, but not limited to, suspending agents, dispersing or wetting agents, emulsifying agents, demulcents, preservatives, buffers, salts, flavorings, coloring agents, and sweetening agents. Oily suspensions may further comprise a thickening agent. Known suspending agents include, but are not limited to, sorbitol syrup, hydrogenated edible fats, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, and cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose. Known dispersing or wetting agents include, but are not limited to, naturally-occurring phosphatides such as lecithin, condensation products of an alkylene oxide with a fatty acid, with a long chain aliphatic alcohol, with a partial ester derived from a fatty acid and a hexitol, or with a partial ester derived from a fatty acid and a hexitol anhydride (e.g., polyoxyethylene stearate, heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate, and polyoxyethylene sorbitan monooleate, respectively). Known emulsifying agents include, but are not limited to, lecithin, and acacia. Known preservatives include, but are not limited to, methyl, ethyl, or n- propyl-para- hydroxybenzoates, ascorbic acid, and sorbic acid. Powdered and granular formulations of a pharmaceutical preparation of the present invention may be prepared using known methods. Such formulations may be administered directly to a subject, used, for example, to form tablets, to fill capsules, or to prepare an aqueous or oily suspension or solution by addition of an aqueous or oily vehicle thereto. Each of these formulations may further comprise one or more of dispersing or wetting agent, a suspending agent, and a preservative. Additional excipients, such as fillers and sweetening, flavoring, or coloring agents, may also be included in these formulations. A pharmaceutical composition of the present invention may also be prepared, packaged, or sold in the form of oil-in-water emulsion or a water-in-oil emulsion. The oily phase may be a vegetable oil such as olive or arachis oil, a mineral oil such as liquid paraffin, or a combination of these. Such compositions may further comprise one or more emulsifying agents such as naturally occurring gums such as gum acacia or gum tragacanth, naturally- occurring phosphatides such as soybean or lecithin phosphatide, esters or partial esters Attorney Docket No.046531-5034-00WO derived from combinations of fatty acids and hexitol anhydrides such as sorbitan monooleate, and condensation products of such partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. These emulsions may also contain additional ingredients including, for example, sweetening or flavoring agents. Methods for impregnating or coating a material with a chemical composition are known in the art, and include, but are not limited to methods of depositing or binding a chemical composition onto a surface, methods of incorporating a chemical composition into the structure of a material during the synthesis of the material (i.e., such as with a physiologically degradable material), and methods of absorbing an aqueous or oily solution or suspension into an absorbent material, with or without subsequent drying. The regimen of administration may affect what constitutes an effective amount. The therapeutic formulations may be administered to the subject either prior to or after a diagnosis of disease. Further, several divided dosages, as well as staggered dosages may be administered daily or sequentially, or the dose may be continuously infused, or may be a bolus injection. Further, the dosages of the therapeutic formulations may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation. Administration of the compositions of the present invention to a subject, preferably a mammal, more preferably a human, may be carried out using known procedures, at dosages and for periods of time effective to prevent or treat disease. An effective amount of the therapeutic compound necessary to achieve a therapeutic effect may vary according to factors such as the activity of the particular compound employed; the time of administration; the rate of excretion of the compound; the duration of the treatment; other drugs, compounds or materials used in combination with the compound; the state of the disease or disorder, age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors well-known in the medical arts. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. A non-limiting example of an effective dose range for a therapeutic compound of the present invention is from about 1 and 5,000 mg / kg of body weight / per day. One of ordinary skill in the art would be able to study the relevant factors and make the determination regarding the effective amount of the therapeutic compound without undue experimentation. The compound may be administered to a subject as frequently as several times daily, Attorney Docket No.046531-5034-00WO or it may be administered less frequently, such as once a day, once a week, once every two weeks, once a month, or even less frequently, such as once every several months or even once a year or less. It is understood that the amount of compound dosed per day may be administered, in non-limiting examples, every day, every other day, every 2 days, every 3 days, every 4 days, or every 5 days. For example, with every other day administration, a 5 mg per day dose may be initiated on Monday with a first subsequent 5 mg per day dose administered on Wednesday, a second subsequent 5 mg per day dose administered on Friday, and so on. The frequency of the dose will be readily apparent to the skilled artisan and will depend upon any number of factors, such as, but not limited to, the type and severity of the disease being treated, the type and age of the animal, etc. Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular subject, composition, and mode of administration, without being toxic to the subject. A medical doctor, e.g., physician or veterinarian, having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds of the present invention employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In particular embodiments, it is especially advantageous to formulate the compound in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subjects to be treated; each unit containing a predetermined quantity of therapeutic compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the present invention are dictated by and directly dependent on (a) the unique characteristics of the therapeutic compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding / formulating such a therapeutic compound for the treatment of a disease in a subject. In one embodiment, the compositions of the present invention are administered to the subject in dosages that range from one to five times per day or more. In another embodiment, the compositions of the present invention are administered to the subject in range of dosages that include, but are not limited to, once every day, every two, days, every three days to once a week, and once every two weeks. It will be readily apparent to one skilled in the art that the Attorney Docket No.046531-5034-00WO frequency of administration of the various combination compositions of the present invention will vary from subject to subject depending on many factors including, but not limited to, age, disease or disorder to be treated, gender, overall health, and other factors. Thus, the invention should not be construed to be limited to any particular dosage regime and the precise dosage and composition to be administered to any subject will be determined by the attending physical taking all other factors about the subject into account. Compounds of the present invention for administration may be in the range of from about 1 mg to about 10,000 mg, about 20 mg to about 9,500 mg, about 40 mg to about 9,000 mg, about 75 mg to about 8,500 mg, about 150 mg to about 7,500 mg, about 200 mg to about 7,000 mg, about 3050 mg to about 6,000 mg, about 500 mg to about 5,000 mg, about 750 mg to about 4,000 mg, about 1 mg to about 3,000 mg, about 10 mg to about 2,500 mg, about 20 mg to about 2,000 mg, about 25 mg to about 1,500 mg, about 50 mg to about 1,000 mg, about 75 mg to about 900 mg, about 100 mg to about 800 mg, about 250 mg to about 750 mg, about 300 mg to about 600 mg, about 400 mg to about 500 mg, and any and all whole or partial increments there between. In some embodiments, the dose of a compound of the present invention is from about 1 mg and about 2,500 mg. In some embodiments, a dose of a compound of the present invention used in compositions described herein is less than about 10,000 mg, or less than about 8,000 mg, or less than about 6,000 mg, or less than about 5,000 mg, or less than about 3,000 mg, or less than about 2,000 mg, or less than about 1,000 mg, or less than about 500 mg, or less than about 200 mg, or less than about 50 mg. Similarly, in some embodiments, a dose of a second compound (i.e., a drug used for treating the same or another disease as that treated by the compositions of the present invention) as described herein is less than about 1,000 mg, or less than about 800 mg, or less than about 600 mg, or less than about 500 mg, or less than about 400 mg, or less than about 300 mg, or less than about 200 mg, or less than about 100 mg, or less than about 50 mg, or less than about 40 mg, or less than about 30 mg, or less than about 25 mg, or less than about 20 mg, or less than about 15 mg, or less than about 10 mg, or less than about 5 mg, or less than about 2 mg, or less than about 1 mg, or less than about 0.5 mg, and any and all whole or partial increments thereof. In one embodiment, the present invention is directed to a packaged pharmaceutical composition comprising a container holding a therapeutically effective amount of a compound or conjugate of the present invention, alone or in combination with a second pharmaceutical agent; and instructions for using the compound or conjugate to treat, prevent, or reduce one or more symptoms of a disease in a subject. Attorney Docket No.046531-5034-00WO The term “container” includes any receptacle for holding the pharmaceutical composition. For example, in one embodiment, the container is the packaging that contains the pharmaceutical composition. In other embodiments, the container is not the packaging that contains the pharmaceutical composition, i.e., the container is a receptacle, such as a box or vial that contains the packaged pharmaceutical composition or unpackaged pharmaceutical composition and the instructions for use of the pharmaceutical composition. Moreover, packaging techniques are well known in the art. It should be understood that the instructions for use of the pharmaceutical composition may be contained on the packaging containing the pharmaceutical composition, and as such the instructions form an increased functional relationship to the packaged product. However, it should be understood that the instructions may contain information pertaining to the compound’s ability to perform its intended function, e.g., treating or preventing a disease in a subject, or delivering an imaging or diagnostic agent to a subject. Routes of administration of any of the compositions of the present invention include oral, nasal, rectal, parenteral, sublingual, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal, and (trans)rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. Suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration and the like. It should be understood that the formulations and compositions that would be useful in the present invention are not limited to the particular formulations and compositions that are described herein. These methods described herein are by no means all-inclusive, and further methods to suit the specific application will be apparent to the ordinary skilled artisan. Moreover, the effective amount of the compositions can be further approximated through analogy to compounds known to exert the desired effect. EXPERIMENTAL EXAMPLES The invention is further described in detail by reference to the following experimental Attorney Docket No.046531-5034-00WO examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure. Example 1: A family of antibiotics that evades resistance by binding polyprenyl phosphates Accessing microbial NPs from their native producers is hampered by a lack of expression of most biosynthetic gene clusters (BGCs) under laboratory conditions (Bodor A. et al., 2020, Rev Environ Sci Bio, 19:1-22; Covington B. C. et al., 2021, Annu Rev Biochem, 90:763-788). To address this bottleneck, the present studies have developed a biology-free discovery approach where BGC products are bioinformatically generated and their structures are produced by total chemical synthesis. These molecules were termed synthetic bioinformatic NPs (synBNPs) (Chu J. et al., 2016, Nat Chem Biol, 12:1004-1006). This method provides access to bioactive small molecules inspired by BGCs whose products are otherwise inaccessible via culture-dependent methods (Chu J. et al., 2020, J Am Chem Soc, 142:14158-14168). As shown in Figure 1, non-ribosomal polypeptide synthetase (NRPS) BGCs acquired from JGI and GenBank were bioinformatically queried with the linear polypeptide sequence of cilagicin, those BGCs generated to share >50% of amino acids in the same positions were pursued for synBNP. Three BGCs met the criteria of this search and were bioinformatically generated and built using total synthesis. The resultant synBNP molecules were assayed for antibiotic activity and antibiotic resistance profile and it was found that paenilagicin and virgilagicin evaded resistance development while bacilagicin did not. Using a synBNP approach to study NRPS BGCs in sequenced bacterial genomes led to the discovery of the antibiotic cilagicin (1). Cilagicin is a dodeca-lipodepsipeptide with potent activity against a number of clinically relevant multidrug resistant Gram-positive pathogens (Wang Z. et al., 2022, Science, 376:991-996). Cilagicin’s antibacterial activity results from its ability to bind both undecaprenyl phosphate (C55:P) and undecaprenyl pyrophosphate (C55:PP). These two polyprenyl phosphates are essential chaperones involved Attorney Docket No.046531-5034-00WO in moving glycopeptide subunits to the outside of the cell where they are polymerized to build the cell wall (Manat G. et al., 2014, Microb Drug Resist, 20:199-214). The absence of observed resistance to cilagicin in both clinical isolates and laboratory experiments is likely due to its ability to bind to two distinct molecular targets. Cilgacin’s ability to evade antibiotic resistance makes this class of antibiotics appealing to explore in more detail for clinical development purposes. The herein described studies sought to identify additional synBNP antibiotics that evade resistance by first bioinformatically screening and then synthesizing cilagicin-like structures generated from NRPS BGCs found in sequenced bacterial genomes. The efforts led to the discovery of three antibiotics, two of which (paenilagicin (2) and virgilagicin (4)) sequester both C55:P and C55:PP and do not develop resistance even after prolonged antibiotic exposure. The cilagicin (cil) BGC was originally selected as a synBNP target based on a phylogenetic analysis of condensation starter (Cs) domains. The cil Cs domain was related to domains from known antibiotic producing BGCs but was associated with a clade that did not contain sequences from any previously characterized BGCs (Figure 2). To identify structure generations that could serve as synBNP targets to produce antibiotics that do not develop resistance, bioinformatically generated NRPS-derived NPs were searched for structures related to cilagicin. NRPS biosynthesis takes place in an assembly line fashion involving distinct modules containing sets of domains that build a product one amino acid at a time. A canonical NRPS extender module contains a minimum of three domains: a thiolation (T) domain that passes the growing polymer from one module to the next, an adenylation (A) domain that selects and activates a specific amino acid substrate and a condensation (C) domain that catalyzes the formation of an amide bond between the new amino acid and the previously assembled portion of the peptide (Miller B. R. et al., 2016, Methods Mol Biol, 1401:3-29). The amino acid used by each adenylation (A) domain can be generated based on 10 amino acid residues that line the substrate binding pocket (Stachelhaus T. et al., 1999, Chem Biol, 6:493-505). For this study, complete NRPS BGCs collected from sequenced bacterial genomes found in the Joint Genome Institute and GenBank databases were used (Sayers E. W. et al., 2023, Nucleic Acids Res, 51:D29-D38; Nordberg H. et al., 2014, Nucleic Acids Res, 42:D26- 31). A-domain substrate binding pockets found in these NRPS systems were compared to a manually curated list of signature sequences collected from characterized NRPS BGCs to generate linear peptide product generations from each BGC. The resulting database of generated peptide sequences was queried with the cilagicin linear peptide sequence and hits Attorney Docket No.046531-5034-00WO were ranked based on the number of positionally identical residues (PIRs) shared with the query sequence (Figure 6 and Figure 7). Two generated products were identical to cilagicin, both of which were generated from BGCs in Paenibacillus mucilaginosus genomes. Only three additional generated NRPS structures shared 7 or more (i.e. >50%) PIRs with cilagicin. There were no generated products that shared 6 PIRs with cilagicin, while there was a large diverse collection of sequences that shared 5 or fewer PIRs with cilagicin. Although not bound by any particular theory, it was hypothesized that the small number of structures sharing >50% PIRs with cilagicin could potentially share a mode of action with cilagicin and additional studies therefore focused on these structures. The BGCs, from which the three potential antibiotics were generated, were found in the sequenced genomes of Paenibacillus puerhi (NZ_WUWM01000006.1), Bacillus cereus (CP068135.1), and Virgibacillus sp. Bac332 (NZ_CP033046.1) (Figure 3). The three generated BGCs were identified to contain either 11 or 12 NRPS modules and were expected to encode unique undeca- and dodeca- peptides. Each linear peptide contained a Thr residue at either the first or second position. As seen in cilagicin, the NPs encoded by these BGCs are cyclized through their C-terminal carboxylates and this conserved N-terminal Thr (Figure 4). While the encoded linear peptides are different lengths, cyclization through the Thr generate an 11 amino acid cilagicin-like macrocycle in each product. In the case of cilagicin, the Cs domain present in the cilC NRPS protein adds a long chain fatty acid to the N-terminus. Notably, the three BGCs identified in this study contained CoA-ligase (CAL) domains in place of a Cs domain (Table 2 through Table 4). Similar to Cs domains, CAL domains append an N-terminal lipid onto the NRPS encoded polypeptides. The absence of a Cs domain in these three BGCs likely explains why they were not identified in the original Cs domain phylogenetic analysis that uncovered the cil BGC. NRPS-derived lipopeptides are often produced with a range of different lipids and bioinformatically generating the exact lipid(s) used in their biosynthesis remains a challenge. In the structure generation analysis, myristic acid was used because it is one of the most common lipids found in lipopeptide secondary metabolites and it displayed potent activity in the original cilagicin study. Based on these bioinformatic arguments, the undeca- and dodeca- lipodepsipeptides generated to arise from the three NRPS BGCs were identified as shown in Figure 4. In reference to the organisms in which these BGCs are found, these structures were named paenilagicin (2), bacilagicin (3) and virgilagicin (4), respectively. A synBNP was generated based on each structure. Bioinformatically generated linear peptides were synthesized using Fmoc-based solid phase peptide synthesis ending with a Attorney Docket No.046531-5034-00WO myristic acid on the N-terminus. Following linear assembly, ester bonds were formed on resin between the threonine side chain and the generated amino acid from the last module in each BGC. Branched linear peptides were released from solid support by HFIP cleavage. Each ring structure was completed in solution via amide coupling between the free amine of the branched amino acid and the carboxylic acid formerly bound to the resin. Cyclized lipodepsipeptides were deprotected in 95% TFA and HPLC purified to yield the final molecular product. All structures were confirmed by HRMS (Figure 7 through Figure 10, Table 5, and Table 7 through Table 12) and by1H and13C NMR (Figure 11 through Figure 13). Each synBNP structure was tested for antibiotic activity against Gram-positive and Gram-negative bacteria as well as human cells (Table 1 and Table 6). As seen with cilagicin, all three synBNPs exhibited activity against clinically relevant gram-positive pathogens. Against most strains, the new compounds showed a slight reduction in potency compared to cilagicin; however, paenilagicin and virgilagicin were slightly more active than cilagicin against Clostridium difficile. Generally, they did not have Gram-negative activity, although paenilagicin, like cilagicin, showed mild activity against Acinetobacter baumannii. No synBNPs inhibited the growth of human cells at the highest concentration tested. Table 1: MIC activity (μg / mL) of synBNPs Cilagicin (1) Paenilagicin (2) Bacilagicin (3) Virgilagicin (4)Gram-Positive Staphylococcus aureus 1 2 2 4 Enterococcus faecium 2 2 4 8 Enterococcus faecalis 1 2 2 4 Clostridium difficile 4 2 4 2 Streptococcus agalactiae 1 2 4 4 ram-Negative Acinetobacter baumannii 4 8 >64 >64 Escherichia coli >64 >64 >64 >64 Human Cells HEK293 (IC50) >64 >64 >64 >64 Table 2: CA-01 biosynthetic gene cluster gene annotations (GenBank Accession # Attorney Docket No.046531-5034-00WO NZ_WUWM01000006.1, region 1). ORF Gene Size (bp) Proposed Function Protein, [Source Organism], Accession number 1 1395 other hypothetical protein, [Paenibacillus puerhi], WP_159882293.1 2 654 other FusB / FusC family EF-G-binding protein, [Paenibacillus puerhi], WP_159882294.1 3 1062 other LLM class flavin-dependent oxidoreductase, [Paenibacillus puerhi], WP_159882295.1 4 570 regulatory TetR / AcrR family transcriptional regulator, [Paenibacillus puerhi], WP_159882296.1 5 177 other hypothetical protein, [Paenibacillus puerhi], WP_159882297.1 6 708 other DUF421 domain-containing protein, [Paenibacillus puerhi], WP_159882298.1 7 1725 other stalk domain-containing protein, [Paenibacillus puerhi], WP_159882299.1 8 1764 other stalk domain-containing protein, [Paenibacillus puerhi], WP_159882300.1 9 648 other DUF1796 family putative cysteine peptidase, [Paenibacillus puerhi], WP_159882301.1 10 1017 other cytochrome d ubiquinol oxidase subunit II, [Paenibacillus puerhi], WP_159882302.1 11 1335 other cytochrome ubiquinol oxidase subunit I, [Paenibacillus puerhi], WP_159882461.1 12 1212 transport MFS transporter, [Paenibacillus puerhi], WP_159882303.1 13 762 transport ABC transporter ATP-binding protein, [Paenibacillus puerhi], WP_159882304.1 14 1929 transport ABC transporter permease, [Paenibacillus puerhi], WP_159882305.1 15 3870 biosynthetic AMP-binding protein, [Paenibacillus puerhi], WP_159882306.1 16 17952 biosynthetic non-ribosomal peptide synthetase, [Paenibacillus puerhi], WP_159882307.1 17 11748 biosynthetic amino acid adenylation domain-containing protein, [Paenibacillus puerhi], WP_235941328.1 18 12726 biosynthetic non-ribosomal peptide synthetase, [Paenibacillus puerhi], WP_159882308.1 19 684 regulatory response regulator transcription factor, [Paenibacillus puerhi], WP_159882309.1 20 1023 regulatory sensor histidine kinase, [Paenibacillus puerhi], WP_159882310.1 21 1203 biosynthetic-additional glycosyltransferase, [Paenibacillus puerhi],WP_159882311.1 22 309 other hypothetical protein, [Paenibacillus puerhi], WP_159882312.1 Attorney Docket No.046531-5034-00WO 23 801 biosynthetic-additional arsenite methyltransferase, [Paenibacillus puerhi],WP_159882313.1 24 1056 other NAD(P) / FAD-dependent oxidoreductase, [Paenibacillus puerhi], WP_159882314.1 25 450 regulatory MarR family winged helix-turn-helix transcriptional regulator, [Paenibacillus puerhi], WP_159882315.1 26 444 other dual specificity protein phosphatase family protein, [Paenibacillus puerhi], WP_159882316.1 27 471 other ArsI / CadI family heavy metal resistance metalloenzyme, [Paenibacillus puerhi], WP_159882317.1 28 426 other arsenate reductase (thioredoxin), [Paenibacillus puerhi], WP_159882318.1 29 1413 other arsenic transporter, [Paenibacillus puerhi], WP_159882319.1 30 324 regulatory metalloregulator ArsR / SmtB family transcription factor, [Paenibacillus puerhi], WP_159882320.1 31 432 other arsenate reductase ArsC, [Paenibacillus puerhi], WP_159882321.1 32 132 other hypothetical protein, [Paenibacillus puerhi], WP_268893700.1 33 417 other VOC family protein, [Paenibacillus puerhi], WP_159882323.1 34 576 other dihydrofolate reductase family protein, [Paenibacillus puerhi], WP_159882324.1 35 630 other isochorismatase family protein, [Paenibacillus puerhi], WP_159882325.1 36 588 other GH32 C-terminal domain-containing protein, [Paenibacillus puerhi], WP_235941329.1 37 984 other glycoside hydrolase family 32 protein, [Paenibacillus puerhi], WP_235941330.1 38 1623 regulatory response regulator, [Paenibacillus puerhi], WP_159882326.1 39 282 other GH32 C-terminal domain-containing protein, [Paenibacillus puerhi], WP_235941338.1 Table 3: CA-02 biosynthetic gene cluster gene annotations (GenBank Accession # CP068135.1, region 11). ORF Gene Size (bp) Proposed Function Protein Function, [Source Organism], Accession number 1 1551 other glycine betaine transporter OpuD, [Bacillus Cerus], QQU30007.1 2 870 other GNAT family N-acetyltransferase, [Bacillus Cerus], QQU30008.1 3 3045 other NEAT domain-containing protein, [Bacillus Cerus], n / a Attorney Docket No.046531-5034-00WO 4 153 other sporulation protein YhbH, [Bacillus Cerus], n / a 5 168 other hypothetical protein, [Bacillus Cerus], QQU30009.1 6 1548 other recombinase family protein, [Bacillus Cerus], QQU30010.1 7 3027 transport efflux RND transporter permease subunit, [Bacillus Cerus], QQU30011.1 8 1926 transport ABC transporter permease, [Bacillus Cerus], QQU30012.1 9 765 transport ABC transporter ATP-binding protein, [Bacillus Cerus], QQU30013.110 702 biosynthetic-additional 4'-phosphopantetheinyl transferase superfamilyprotein, [Bacillus Cerus], QQU30014.111 738 biosynthetic-additional thioesterase, [Bacillus Cerus], QQU30015.112 1023 other sensor histidine kinase, [Bacillus Cerus], QQU30016.1 13 684 regulatory response regulator transcription factor, [Bacillus Cerus], QQU30017.1 14 12603 biosynthetic amino acid adenylation domain-containing protein, [Bacillus Cerus], QQU30018.1 15 12975 biosynthetic amino acid adenylation domain-containing protein, [Bacillus Cerus], QQU30019.1 16 11559 biosynthetic amino acid adenylation domain-containing protein, [Bacillus Cerus], QQU30020.1 17 10107 biosynthetic amino acid adenylation domain-containing protein, [Bacillus Cerus], QQU30021.1 18 3849 biosynthetic AMP-binding protein, [Bacillus Cerus], QQU30022.1 19 1272 transport MFS transporter, [Bacillus Cerus], QQU30023.1 20 1164 other sporulation protein YhbH, [Bacillus Cerus], QQU30024.1 21 1896 other PrkA family serine protein kinase, [Bacillus Cerus], QQU30025.122 2070 biosynthetic-additional EAL domain-containing protein, [Bacillus Cerus],QQU30026.1 23 489 other tRNA (uridine(34) / cytosine(34) / 5- carboxymethylaminomethyluridine(34)-2'-O)- methyltransferase TrmL, [Bacillus Cerus], QQU30027.1 24 888 other amidase domain-containing protein, [Bacillus Cerus], QQU30028.1 25 1143 other tRNA epoxyqueuosine(34) reductase QueG, [Bacillus Cerus], QQU30029.1 26 651 other DsbA family protein, [Bacillus Cerus], QQU30030.1 27 777 other transglycosylase domain-containing protein, [Bacillus Cerus], QQU30031.1 28 462 other NUDIX hydrolase, [Bacillus Cerus], QQU30032.1 29 720 other YebC / PmpR family DNA-binding transcriptional regulator, [Bacillus Cerus], QQU30033.1 Attorney Docket No.046531-5034-00WO 30 321 other DUF3884 family protein, [Bacillus Cerus], QQU30007.1 Table 4: CA-03 biosynthetic gene cluster gene annotations (GenBank Accession # NZ_CP033046.1, region 3). ORF Gene Size (bp) Proposed Function Protein Function, [Source Organism], Accession number 1 576 regulatory Ada metal-binding domain-containing protein, [Virgibacillus sp. Bac332], WP_121604742.1 2 216 other hypothetical protein, [Virgibacillus sp. Bac332], WP_121604743.1 3 198 other hypothetical protein, [Virgibacillus sp. Bac332], WP_121604744.1 4852 biosynthetic-additional formyltetrahydrofolate deformylase, [Virgibacillussp. Bac332], WP_162986377.1 5 675 regulatory helix-turn-helix transcriptional regulator, [Virgibacillus sp. Bac332], WP_121604746.1 61305 biosynthetic-additional SidA / IucD / PvdA family monooxygenase,[Virgibacillus sp. Bac332], WP_121604747.1 71278 biosynthetic-additional aminotransferase class III-fold pyridoxal phosphate-dependent enzyme, [Virgibacillus sp. Bac332], WP_121604748.1 81164 biosynthetic-additional FAD-dependent oxidoreductase, [Virgibacillus sp.Bac332], WP_161629296.1 9 1089 other SIS domain-containing protein, [Virgibacillus sp. Bac332], WP_026682877.1 10 1098 transport ABC transporter substrate-binding protein, [Virgibacillus sp. Bac332], WP_026682876.1 11 816 biosynthetic-additional cupin domain-containing protein, [Virgibacillus sp.Bac332], WP_051388458.1 12 1623 biosynthetic-additional class I tRNA ligase family protein, [Virgibacillus sp.Bac332], WP_162986378.1 13 996 other aspartate kinase, [Virgibacillus sp. Bac332], WP_121604750.1 14 900 other DNA-3-methyladenine glycosylase, [Virgibacillus sp. Bac332], WP_121604751.1 15 522 other methylated-DNA--[protein]-cysteine S- methyltransferase, [Virgibacillus sp. Bac332], WP_121604752.1 16 1254 biosynthetic-additional amino acid permease, [Virgibacillus sp. Bac332],WP_034679745.1 17 969 biosynthetic-additional alpha / beta hydrolase, [Virgibacillus sp. Bac332],WP_226983629.1 18 3819 biosynthetic AMP-binding protein, [Virgibacillus sp. Bac332], WP_121604753.1 19 5115 biosynthetic non-ribosomal peptide synthetase, [Virgibacillus sp. Bac332], WP_121604754.1 Attorney Docket No.046531-5034-00WO 20 11556 biosynthetic non-ribosomal peptide synthetase, [Virgibacillus sp. Bac332], WP_162986379.1 21 13017 biosynthetic amino acid adenylation domain-containing protein, [Virgibacillus sp. Bac332], WP_240455720.1 22 12555 biosynthetic non-ribosomal peptide synthetase, [Virgibacillus sp. Bac332], WP_121604757.1 23 687 regulatory response regulator transcription factor, [Virgibacillus sp. Bac332], WP_034679502.1 24 1014 regulatory sensor histidine kinase, [Virgibacillus sp. Bac332], WP_026682509.1 25 747 biosynthetic-additional thioesterase domain-containing protein,[Virgibacillus sp. Bac332], WP_162986380.1 26 696 biosynthetic-additional 4'-phosphopantetheinyl transferase superfamilyprotein, [Virgibacillus sp. Bac332], WP_121604759.1 27 765 transport ABC transporter ATP-binding protein, [Virgibacillus sp. Bac332], WP_026682512.1 28 1926 transport ABC transporter permease, [Virgibacillus sp. Bac332], WP_121604760.1 29 3006 transport efflux RND transporter permease subunit, [Virgibacillus sp. Bac332], WP_121604761.1 30 984 transport ABC transporter ATP-binding protein, [Virgibacillus sp. Bac332], WP_121604762.1 31 774 other ABC transporter permease, [Virgibacillus sp. Bac332], WP_026682516.1 32 276 transport hypothetical protein, [Virgibacillus sp. Bac332], WP_240455721.1 33 633 other hypothetical protein, [Virgibacillus sp. Bac332], WP_121604763.1 34 948 other oxidoreductase, [Virgibacillus sp. Bac332], WP_121604764.1 35 861 other hypothetical protein, [Virgibacillus sp. Bac332], WP_121604765.1 36 315 other hypothetical protein, [Virgibacillus sp. Bac332], WP_026682519.1 37 507 other matrixin family metalloprotease, [Virgibacillus sp. Bac332], WP_121604766.1 38 618 other hypothetical protein, [Virgibacillus sp. Bac332], WP_051388429.1 39 489 other DUF4362 domain-containing protein, [Virgibacillus sp. Bac332], WP_162986381.1 40 565 other transposase, [Virgibacillus sp. Bac332], n / a 41 204 other hypothetical protein, [Virgibacillus sp. Bac332], WP_240455722.1 42 366 other hypothetical protein, [Virgibacillus sp. Bac332], WP_240455723.1 Table 5: High-resolution mass spectrometry* data for cilagicin analogs. *All HRMS data Attorney Docket No.046531-5034-00WO were collected in positive ionization mode with a mass range from m / z 200 to 2500. Molecules Chemical Formula Theoretical Observed Error [M+H]+[M+H]+(ppm) Paenilagicin C65H99N13O19 1366.72 1366.7176 1.7 Bacilagicin C69H104N16O23 1525.75 1525.7466 2.2 Virgilagicin C65H106N18O19 1443.79 1443.7923 1.5 Table 6: Bacterial strains, human cell lines and corresponding culture conditions. *LBM media was a brain heart infusion media derivate which supplemented with 5 ug / mL hemin, 1 mg / mL maltose, 1 mg / mL cellobiose and 500 ug / mL L-cysteine. Name of Cell Type Strain Media Culture Condition Bacterial Species Staphylococcus aureus USA300 LB 37 °C, aerobic Enterococcus faecium AR807 LB Enterococcus faecalis AR785 LB Streptococcus agalactiae BAA2675 LB Acinetobacter baumannii ATCC17978 LB Escherichia coli ATCC25922 LB Clostridium difficile HM746 LMB 37 °C, 5% H2, 5% CO2, 90% N2 Human Cells Human Kidney Cells HEK293 DMEM, 10% 37 °C, 5% CO2 Fetal Bovine Serum, L- Glutamine, Penicillin / Streptavidin Table 7: MS-MS analysis of natural cilagicin analog synBNPs of patent ions of Paenilagicin. Ion Formula Calculated Observed m / z RDB Δ ppm m / z [M+H]+C65H100N13O19+1366.7253 1366.7137 23.0 -8.48[M+H-H2O]+ C65H98N13O18+ 1348.7147 1348.7084 24.0-4.73[M+2H]2+C65H101N13O192+683.8663 683.8619 22.0 -6.41 Table 8: Assignment of MS / MS fragment ions of Paenilagicin. Ion Formula Calculated m / z Observed m / z RDB Δ ppm a, X+C58H94N13O18+1253.6412 1253.6317 21.5 -7.63 b, X+C50H80N11O16+1090.5779 1090.5728 16.5 -4.71 c, X+C36H59N8O12+795.4247 795.4175 11.5 -9.05 d, X+C34H56N7O11+738.4032 738.3977 10.5 -7.48 e, X+C26H44N3O7+510.3174 510.3166 6.5 -1.43 f, X+C18H32NO2+294.2428 294.2413 3.5 -5.08 g, X+C8H13N2O5+217.0819 217.0819 3.5 -0.05 h, [X+H]+C43H62N11O15+972.4421 972.4387 19.0 -3.46 Attorney Docket No.046531-5034-00WO i, X+C22H39N2O4+395.2904 395.2895 4.5 -2.25 j, [X+H]+C39H57N10O12+857.4152 857.4040 17.0 -13.05 k, X+C11H21N3O2+228.1707 228.1710 3.0 1.35 l, X+C5H11N2O+115.0866 115.0859 2.0 -6.33 m, [X+H]+C9H11NO3+182.0812 182.0816 5.0 2.41 n, [X+H- C8H10NO+136.0757 136.0749 5.0 -5.56 CO]+Table 9: MS-MS analysis of natural cilagicin analog synBNPs of patent ions of Bacilagicin. Ion Formula Calculated m / z Observed m / z RDB Δ ppm [M+H]+C69H105N16O23+1525.7533 1525.7446 26.0 -5.72 [M+2H]2+C69H106N16O232+1526.7605 763.3773 25.0 -3.87 Table 10: Assignment of MS / MS fragment ions of Bacilagicin. Ion Formula Calculated m / z Observed m / z RDB Δ ppm a, X+C64H96N15O22+1426.6849 1426.6801 24.5 -3.38 b, [X+H-CO]+C4H10N+72.0808 72.0806 1.0 -2.15 c, X+C60H96N15O21+1362.6900 1362.6809 20.5 -6.66 d, [X+H-CO]+C8H10NO+136.0757 136.0756 5.0 -1.04 e, X+C55H87N14O20+1263.6216 1263.6330 19.5 9.09 f, X+C53H84N13O19+1206.6001 1206.5938 18.5 -5.18 g, X+C16H22N3O4+320.1604 320.1617 7.5 3.76 h, X+C49H79N12O16+1091.5732 1091.5677 16.5 -5.00 I, X+C20H27N4O7+435.1874 435.1866 9.5 -1.96 j, X+C52H74N15O20+1228.5229 1228.5144 23.5 -6.90 k, X+C17H32NO3+298.2376 298.2371 2.5 -1.77 l, X+C47H65N14O19+1129.4545 1129.4570 22.5 2.20 m, [X+H-CO]+C16H32NO2+270.2428 270.2430 2.0 1.02 n, X+C11H13N2O3+221.0921 221.0925 6.5 2.05 o, [X+H]+C2H6NO+60.0444 60.0444 1.0 0.77 Table 11: MS-MS analysis of natural cilagicin analog synBNPs of patent ions of Virgilagicin. Ion Formula Calculated m / z Observed m / z RDB Δ ppm [M+H]+C65H106N18O19+1443.7954 1443.7885 22.0 -4.81 [M+2H]2+C65H108N18O192+742.3694 722.3970 21.0 -6.06 Table 12: Assignment of MS / MS fragment ions of Virgilagicin. Ion Formula Calculated m / z Observed m / z RDB Δ ppm a, X+C49H75N12O15+1071.5469 1071.5500 18.5 2.85 b, X+C40H66N11O13+ 908.4836 908.4829 13.5 -0.83 c, [X+H- C8H10NO+136.0757 136.075 5.0 -0.50 CO]+d, X+C38H63N10O12+851.4621 851.4586 12.5 -4.15 Attorney Docket No.046531-5034-00WO e, X+C28H49N6O6+565.3708 565.3662 7.5 -8.21 f, X+C24H46N5O4+468.3544 468.3567 4.5 4.83 g, [X-HxO]+C24H44N5O3+450.3439 450.3449 5.5 2.28 h, [X-H2O]+C18H32NO2+294.2428 294.2429 3.5 0.53 i, [X+H]+C16H33N6O4+373.2558 373.2582 4.0 6.55 k, [X+H- C4H10N+72.0808 72.0806 1.0 -3.09 CO]+j, [X+H]+C11H24N5O3+274.1874 274.1884 3.0 3.59 l, [X+H- C11H21N4O3+257.1608 257.1606 4.0 -0.91 NH3]+Cilagicin is a bi-functional antibiotic that is able to sequester both C55:P and C55:PP. Addition of excess C55:P or C55:PP to culture media suppresses cilagicin’s activity by sequestering the antibiotic away from the cell wall of target bacteria. The role of C55:P and C55:PP was explored in the activity of each synBNP by determining its MIC against Staphylococcus aureus in culture broth supplemented with varying ratios of antibiotic and polyprenyl phosphate (Figure 5). Like cilagicin, the activity of paenilagicin and virgilagicin were suppressed by C55:P and C55:PP in a dose dependent manner, indicating these structures retain both polyprenyl phosphates as molecular targets. The activity of bacilagicin was only suppressed by C55:P. In the case of C55:PP, the MIC of bacilagicin remained largely unchanged even when five-fold molar excess of C55:PP was added to the assay media, indicating that bacilagicin does not sequester C55:PP (Figure 5A). Cilagicin’s antibacterial activity was completely suppressed at less than a 2-fold molar excess of C55:P or C55:PP. When suppression of antibacterial activity was observed for the new synBNPs it required ~3-fold molar excess of a polyprenyl phosphate. This difference in polyprenyl phosphate affinity could explain the lower potency seen for these antibiotics. The ability to bind two molecular targets (C55:P and C55:PP) is what likely enables cilagicin to avoid the development of antibiotic resistance even after prolonged exposure. Other antibiotics that bind a single polyprenyl phosphate molecule (e.g., amphomycin and bacitracin) typically develop resistance quickly (Radeck J. et al., 2016, Mol Microbiol, 100:607-620; Diehl A. et al.2020, Antibiotics (Basel), 9). As such, bacilagicin would no longer be able to avoid resistance development during long-term exposure to a pathogen. To test this, it was attempted to raise S. aureus antibiotic resistant mutants by daily serial passage for 14 days in the presence of sub-MIC (0.5x MIC) levels of paenilagicin, bacilagicin, virgilagicin, cilagicin, or amphomycin. Cultures exposed to paenilagicin or virgilagicin, like those exposed to cilagicin, did not develop antibiotic resistance. By contrast, cultures exposed to bacilagicin, quickly showed a 4-fold increase in MIC, following a similar pattern to Attorney Docket No.046531-5034-00WO amphomycin (Figure 5B). Although not bound by any particular theory, these results reinforced the hypothesis that sequestration of both C55:P and C55:PP provided a unique antibacterial mechanism against which it was difficult for pathogens to develop resistance. The structures of these polyprenyl phosphate binding antibiotics showed the most variability in the region surrounding the site of cyclization (Figure 4B). This variable region included the three C-terminal residues of each peptide and the residues adjacent to the conserved Thr. The central region of each macrocycle is more highly conserved. In fact, these 10-membered macrocycles all contained a “DGnxGY” motif that is important for target engagement and therefore potentially useful for guiding the discovery of additional polyprenyl phosphate binding antibiotics in the future. A key difference between bacilagicin, which only binds C55:P, and the other structures in this family that bind both C55:P and C55:PP was the absence of the positively charged residue at position 11. While additional extensive SAR study focuses on determination of the role of this residue in target engagement, the extra positive charge is important for binding the additional negative charge found on the pyrophosphate in C55:PP. No known antibiotics share the “DGnxGY” motif. The closest match is in locillomycin; however, the stereochemistry of multiple residues is inverted in this structure (Luo C. et al., 2015, Appl Environ Microbiol, 81:6601-6609.). Locillomycin also contains a 9 membered macrocycle in place of the 11 membered ring seen in the polyprenyl phosphate binding synBNPs that were identified. Not only does locillomycin differ in structure from these antibiotics, but biosynthetically it arises from the repetitive use of some NRPS modules making the BGC much smaller than those described here. The molecular target of locillomycin has not been reported. While cilagicin is a promising candidate for the development of antibiotics that can overcome resistance mechanisms plaguing the current arsenal of approved drugs, additional studies focus on expanding the available structural diversity within the cilagicin family by bioinformatically screening sequenced bacterial genomes for BGCs generated to encode cilagicin-like structures. This search led to synthesis of three additional members of this mechanistically novel class of antibiotics. As seen with cilagicin, two of these structures do not develop resistance even after extended antibiotic exposure. These structures provide alternative drug development candidates. Coupling synBNP methods with the targeted search of databases comprised of bioinformatically generated BGC product structures is now a straightforward and broadly applicable approach for identifying bioactive small molecules with specific desirable features (Li L. et al., 2022, Nat Microbiol, 7:120-131). Attorney Docket No.046531-5034-00WO In summary, Cilagicin is a Gram-positive active antibiotic that has a dual polyprenyl phosphate binding mechanism, which impedes resistance development. The present studies bioinformatically screened generated non-ribosomal polypeptide synthetase encoded structures to search for antibiotics that might similarly avoid resistance development. Synthesis and bioactivity screening of the identified generated structures led to three antibiotics that are active against multidrug-resistant Gram-positive pathogens, two of which, paenilagicin and virgilagicin, did not develop resistance even after prolonged antibiotic exposure. Methods General Experimental Procedures and Materials: All reagents and solvents were purchased from commercial sources and used without further purification. Solvents used for chromatography were HPLC grade or higher. Preparative HPLC was performed on an CombiFlash EZ Prep purification system with UV detection and equipped with a Phenomenex Luna 5μm C18 prepHPLC column using a dual solvent system (A / B: water / acetonitrile, supplemented with 0.1% (v / v) formic acid). HRMS and MS / MS data were acquired on a SCIEX ExionLC UPLC coupled to an X500R QTOF mass spectrometer, equipped with a Phenomonex Kinetex PS C18100 Å column (2.1 x 50 mm, 2.6 µm) and operated by SCIEXOS software.1H NMR and13C NMR spectra were acquired at room temperature on a Bruker Avance DMX 600 MHz spectrometer (The Rockefeller University, New York, NY) equipped with cryogenic probes, operating at 600 MHz for1H and at 150 MHz for13C and spectra were analyzed using MestReNova software (version 14.3.0-30573). Chemical shift values were reported in ppm and referenced to residual solvent signals, for1H NMR: DMSO-d6 = 2.54 ppm; for13C NMR: DMSO-d6 = 40.45 ppm; CD3OD,1H: 3.31 ppm;13C: 49.0 ppm. Identification and bioinformatic analysis of natural cilagicin biosynthetic gene clusters (BGC): Sequenced nonribosomal peptide synthetase (NRPS) BGCs were collected from the bacterial genome databases JGI and GenBank. BGCs without clearly defined starting (condensation start (Cs) or CoA Ligase (CAL)) and ending (thioesterase (TE)) domains were removed from the collection. For the remaining complete sequenced NRPS BGCs, the 10 amino acids that make up each adenylation (A)-domain binding pocket (i.e., amino acids 235, 236, 239, 278, 299, 301, 322, 330, 331, and 517) were identified using a curated list of A-Domain substrate signatures to generate the substrate of each BGC A- domain. These A-Domain signatures allowed to make a linear polypeptide sequence Attorney Docket No.046531-5034-00WO generation for each NRPS BGC in the collection. Using the linear polypeptide sequence of cilagicin as a query term, NRPS BGCs were ranked by their linear polypeptide sequence similarity to cilagicin. BGCs in the resultant list that shared ≥50% polypeptide sequence similarity to cilagicin that was deemed congeners. This search yielded two BGCs from Paenibacillus mucilaginosus genomes that shared 100% polypeptide sequence identity to cilagicin. Three BGCs were found to share 7 or more (≥58%) of the 12 amino acid positions in cilagicin. The remaining BGCs from the search shared 5 or fewer (≤42%) amino acid positions with cilagicin. The three BGCs with ≥50% polypeptide sequence similarity to cilagicin were carried forward as the congener BGCs investigated in this study. Solid Phase Peptide Synthesis: Natural cilagicin analogs characterized in this study were synthesized using standard Fmoc-based solid-phase peptide synthesis (SPPS) methods on 2-chlorotrityl chloride resin. All peptides were synthesized starting from the penultimate module’s amino acid, for paenilagicin this was ornithine, for bacilagicin this was serine, and for and virgilagicin this was arginine.2-cholorotrityl resin pre-loaded with the appropriate amino acid was swollen in DCM for 30 minutes at room temperature then drained and washed with DMF (3 mL, 3x). Subsequent couplings were carried out using Fmoc-protected amino acids (or a fatty acid) (3 equiv. relative to resin loading) mixed with HATU (3 equiv.) and DIPEA (3 equiv.) in DMF (5 mL). Each coupling reaction was carried out for 45 minutes at room temperature then washed with DMF (5 mL). Fmoc deprotection was carried out by treating resin-bound peptide with 20% piperidine in DMF (5 mL) for 5 minutes (2x). After deprotection, the resin was then washed with DMF (5 mL, 2x), DCM (5 mL, 2x), and DMF (5 mL, 2x). These steps were repeated for each amino acid and fatty acid to construct the linear peptides. Ester bond formation: Ester bonds were formed between the unprotected threonine hydroxyl and the carboxylic acid of the final module’s amino acid. For paenilagicin and bacilagicin this amino acid is tyrosine. For virgilagicin this amino acid is valine. The resin- bound peptide with a free hydroxyl group was mixed with the appropriate Fmoc-AA (15 equiv.) and DIC (15 equiv.) in 7mL DMF. DMAP (0.5 equiv.) was added to the solution, and gently shaken for ~16 hours at room temperature. Peptide cyclization: Resin-bound linear peptides were cleaved by treating with 20% hexafluroisopropanol (HFIP) in DCM for 1 hour (2x). Crude linear peptides were then collected by filtration and dried under reduced pressure. The cleaved linear peptides were cyclized without purification by resuspending in DMF to 0.002M and then mixing with PyAOP (7 equiv.) and DIPEA (20 equiv.). After 2 hours, reaction was transferred to a Attorney Docket No.046531-5034-00WO separatory funnel and ethyl acetate (2.5x volume of DMF) was added. This organic layer was washed with saturated brine (4x), then dried over sodium sulfate. Dried organic layers were filtered and concentrated under reduced pressure to yield crude cyclized peptide. Bulk deprotection: Peptides were dissolved in 6 mL of cleavage cocktail (95% (v / v) TFA, 2.5% (v / v) triisopropylsilane and 2.5% (v / v) water) for 1.25 hours. Cleavage cocktail was evaporated under air flow to yield crude deprotected peptides. Peptide purification: Crude peptides were purified on an Phenomenex Luna 5μm C18 prepHPLC column attached to a CombiFlash EZ Prep purification system using a dual solvent system (A / B: water / acetonitrile, supplemented with 0.1% (v / v) formic acid). Peptide purity and identity were confirmed by UPLC, HRMS, and NMR. Minimum inhibitory concentration (MIC) assay: MIC assays were conducted using the protocol recommended by the Clinical and Laboratory Standards Institute (Clinical; Laboratory Standards, I.; Weinstein, M. P. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Clinical Laboratory Standards Institute, 2018). Culture conditions (temperature, medium) are detailed in Table 6. All compounds were dissolved in sterile DMSO (ATCC, USA) to give a concentration of 6.4 mg / mL. Tested compounds were serially diluted 2-fold in DMSO from a maximum stock concentration of 6.4 mg / mL to 0.006 mg / mL. In a 96-well plate filled with 49 μL fresh growth medium, 1 μL of compound stock dilution was added across wells in a row. An overnight culture of an assay strain was diluted 5,000-fold in fresh medium.50 μL of this inoculum dilution was added into each well, giving a final volume of 100 μL per well. Final assayed concentrations of test compounds ranged from 64 μg / mL to 0.06 μg / mL. MIC values were recorded as the minimum concentration at which no bacterial growth appeared, based on visual inspection, after 16 hours of static incubation at 37 °C. Clostridium difficile plates were statically incubated under anaerobic conditions (Vinyl anaerobic chamber, 37 °C, 5% H2, 5% CO2, 90% N2). MICs were performed in technical duplicate (n=2) and repeated three independent times (n=3). Cytotoxicity assay: The cytotoxicity of natural cilagicin analogs were tested using an MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. HEK293 cells were seeded in a 96-well plate with a density of 5,000 cells / well and cultured in Dulbecco’s Modified Eagle Medium (DMEM) without phenol red and supplemented with 10% fetal bovine serum, 1% Pen / Strep and 1% glutamate for 24 hours at 37 °C with 5% CO2. Serially diluted compounds were added into each well at a final concentration ranging from 64 μg / mL to 0.06 μg / mL. After 48 hours of incubation, the media was removed and 15 μL of Attorney Docket No.046531-5034-00WO freshly prepared MTT solution (5 mg / mL in DPBS) was added to each well. The plates were incubated for 3 hours at 37 °C with 5% CO2after which the MTT solution was removed by aspiration. Precipitated formazan crystals were dissolved by addition of 100 μL of solubilization solution (40% DMF, 16% SDS and 2% acetic acid in H2O). The absorbance of each well was measured at OD570nm using a microplate reader (Infinite 200 PRO, Tecan). All experiments were performed in duplicate (n=2) and repeated three independent times (n=3). Undecaprenyl phosphate feeding assay: The effect of cell wall phospholipids undecaprenyl phosphate (C55:P) and undecaprenyl pyrophosphate (C55:PP) on natural cilagicin analogs’ antibacterial activity was evaluated by co-drying peptide and lipid at molar ratios from 0x to 5x, at 0.5x increments, in plastic tubes in vacuo for 2 hours to completely remove all organic solvent. After drying, compounds were resuspended in scant 2.5 μL methanol, then in 50 μL fresh LB to bring the peptide concentration to 128 μg / mL, followed by vigorous sonication and vortexing.25 μL of this solution was transferred in duplicate to a 384 well plate and serially diluted 2-fold in LB medium from 128 μg / mL to 0.012 μg / mL. An overnight culture of S. aureus USA300 was diluted 5,000-fold in fresh LB medium.12.5 μL of this inoculum dilution was added to each well, giving a final volume of 25 μL per well. Final assayed concentrations of test compounds ranged from 64 μg / mL to 0.06 μg / mL. MIC values were recorded as the minimum concentration at which no bacterial growth appeared, based on visual inspection, after 16 hours of static incubation at 37°C. All assays were run in duplicate (n=2) and repeated two independent times (n=2). Evaluating antibiotic resistance by serial passage in liquid broth: A single colony of S. aureus USA300 was inoculated in 5 mL LB broth and grown overnight at 37 °C with continuous shaking (200 rpm). The overnight culture was then diluted 1:5,000 into fresh LB medium.50 μL aliquots of dilute cells were transferred into individual wells of 96-well plates containing 50 μL of serially diluted cilagicin, natural cilagicin analogs, and amphomycin (Cayman Chemical Company, USA), in accordance with the standard MIC assay set up described above. Stock dilutions of test compounds were prepared fresh daily. Plates were statically incubated at 37 °C. After 24 hours, the MIC was recorded. For the next round of assays, an aliquot from the culture well at half of the MIC from the previous day’s MIC plate was diluted 5000-fold in fresh LB and mixed with serially diluted antibiotics. The MIC was determined as described above. This process was repeated daily for 14 days. For amphomycin, LB medium was supplemented with 100 μg / mL CaCl2-2H2O. Experiments were performed three independent times (n=3). Attorney Docket No.046531-5034-00WO Further analogs were tested, those results are presented in Figures 14, 15, and 16. Example 2: In Vitro Cilagicin Data Additional studies were performed to evaluate the in vitro capabilities of cilagicin (Figure 17 through Figure 28). Safety47 panel results for dodecacilagicin indicated IC50 / EC50> 10 µM for all targets except IC50 for OPRM1 was 3.14 µM (GPCR - opioid receptor), IC50 for CAV1.2 was 5.01 µM (ion channel in cardiac and smooth muscle), IC50for HTR3A was 6.27 µM (ion channel in CNS - serotonin receptor), IC50 for nAChR(a4 / b2) was 2.85 µM (ion channel in CNS - acetylcholine receptor), IC50for COX1 was 8.58 µM, and IC50for COX2 was 9.46 µM (non- kinase enzymes targeted by NSAIDs - lipid mediators involved in pain / inflammation). In contract, Safety47 panel results for cilagicin-BP showed IC50 / EC50> 10 µM for all targets except IC50 for nAChR(a4 / b2) was 6.81 µM (ion channel in CNS - acetylcholine receptor). Example 3: In Vivo Cilagicin Data Furthermore, studies were performed to evaluate the in vivo capabilities of cilagicin (Figure 29 through Figure 31). The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the present invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

Attorney Docket No.046531-5034-00WO CLAIMS What is claimed is:

1. A compound comprising the structure of Formula (I)or a an a a salt, or a derivative thereof; wherein X is selected from the group consisting of O, S, and N(R14); each occurrence of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, and R14is independently selected from the group consisting of hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof; and m is an integer from 0 to 100.

2. The compound of claim 1, wherein the compound comprises the structure of Formula (II)Attorney Docket No.046531-5034-00WOor a racemate, an a a salt, or a derivative thereof; wherein R1, R2, R3, and R4are each independently selected from the group consisting of hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, amino alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof; L represents a group of the formula -C(O)(CH2)p-(Y)q-(CH2)r-H; q and r independently represent an integer having a value between 1 and 20; q represents 0 or 1; and Y represents cis or trans -C(H)=C(H)-.

3. The compound of claim 2, wherein the compound comprises the structure of Formula (IIa)Attorney Docket No.046531-5034-00WOor a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof.

4. The compound of claim 1, wherein the compound comprises the structure of Formula (III) OH Oor a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof; wherein R1is selected from the group consisting of hydrogen, deuterium, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, alkoxycarbonyl, amino, aminoalkyl, aminoaryl, aminoAttorney Docket No.046531-5034-00WO alkyl-aryl, aminoheteroaryl, amino alkyl-heteroaryl, amido, aminoalkenyl, aminoalkynyl, aminoacetate, acyl, hydroxyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, alkoxy, carboxyl, carboxylate, ester, =O, -NO2, -CN, sulfoxy, sulfonyl, alkyl sulfonyl, secondary amide, tertiary amide, an amino acid, and any combinations thereof.

5. The compound of claim 4, wherein the compound comprises the structure of Formula (IIIa)or a racemate, an enantiomer, a diastereomer, a pharmaceutically acceptable salt, or a derivative thereof.

6. The compound of claim 1, wherein m is an integer represented by 0.

7. The compound of claim 1, wherein m is an integer represented by 1.

8. The compound of claim 1, wherein the compound is a zwitterion.

9. The compound of claim 8, wherein the zwitterion comprises at least two positively charged residues and at least two negatively charged residues.

10. The compound of claim 1, wherein the compound comprises at least one amino acid sequence selected at least one amino acid sequence as set forth in SEQ ID NO: 1-Attorney Docket No.046531-5034-00WO 49, amino acid sequence from Figure 2A, at least one amino acid sequence selected from Figure 4A, at least one selected from Figure 6, or any combination thereof.

11. The compound of claim 1, wherein the compound comprises one of the following compounds, or any racemate, enantiomer, diastereomer, pharmaceutically acceptable salt, or derivative thereof: , , O ,Attorney Docket No.046531-5034-00WO .

12. The compound of claim 1, wherein the compound inhibits cell wall biosynthesis.

13. The compound of claim 1, wherein the compound specifically binds at least one undecaprenyl phosphorylate, undecaprenyl pyrophosphate, or a combination thereof.

14. An isolated nucleic acid molecule encoding at least one compound of any one of claims 1-13.

15. A genetically engineered cell capable of producing at least one compound of any one of claims 1-13.

16. A composition comprising at least one compound of any one of claims 1-13, at least one isolated nucleic acid molecule of claim 14, at least one genetically engineered cell of claim 15, or any combination thereof.

17. The composition of claim 16, wherein the composition is a pharmaceutical composition.

18. A method of treating or preventing a bacterial infection in a subject in need thereof, the method comprising administering at least one compound of any one of claims 1- 13, at least one isolated nucleic acid molecule of claim 14, at least one genetically engineered cell of claim 15, at least one composition of claim 16 or 17, or any combination thereof to theAttorney Docket No.046531-5034-00WO subject.

19. The method of claim 18, wherein the subject is exposed to or infected with a pathogen.

20. The method of claim 19, wherein the pathogen is selected from any pathogen listed in Figure 6, Table 1, Table 6, or any combination thereof.

21. The method of claim 19, wherein the pathogen is bacteria.

22. The method of claim 21, wherein the bacteria is selected from the group consisting of drug resistant bacteria, gram positive bacteria, and any combination thereof.

23. The method of claim 21, wherein the bacteria is selected from the group consisting of Bacillus subtilis, Clostridium difficile, Enterococcus faecium, Enterococcus gallinarum, Enterococcus casseliflavus, Escherichia coli, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyrogens, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, Enterobacter species, and any combination thereof.

24. The method of claim 18, wherein the method further comprises administering a second therapeutic.

25. The method of claim 24, wherein the second therapeutic is an antibiotic.

26. A method of inhibiting the growth of or killing a bacterial cell, the method comprising, contacting the bacterial cell with at least one compound of any one of claims 1- 13, at least one isolated nucleic acid molecule of claim 14, at least one genetically engineered cell of claim 15, at least one composition of claim 16 or 17, or any combination thereof.

27. A method of biosynthesizing at least one compound of any one claims 1-13, the method comprising: a) providing a nucleic acid to a host or a growth medium, b) incubating the host in a growth medium; andAttorney Docket No.046531-5034-00WO c) isolating the compound from the host or the growth medium.

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