Antimicrobial peptidomimetics with broad spectrum activity

Abstract

Novel compounds, pharmaceutical compositions, and methods of using such compositions to treat bacterial infections are presented. Sulfonyl-γ-AApeptides exhibiting broad-spectrum activity and high selective index against drug resistant bacterial strains were developed. The sulfonyl-γ-AApeptide AM10 demonstrated effective activity through the mechanism of bacterial membrane disruption and ROS accumulation. The in vivo efficacy against MRSA was evaluated, highlighting the sulfonyl-γ-AApeptide foldamers as promising antimicrobial peptidomimetics escalating bacterial resistance.

Description

ANTIMICROBIAL PEPTIDOMIMETICS WITH BROAD SPECTRUM ACTIVITY CROSS REFERENCE TO RELATED APPLICATIONSThis application is a nonprovisional of and claims priority to U S Provisional Patent Application Serial No. 63 / 765,122, filed February 28, 2025, the contents of which are hereby incorporated by reference into this disclosure.GOVERNMENT SUPPORTThis invention was made with Government support under Grant No 5R01GM150196 and 5R01AI152416 awarded by the National Institutes of Health (NIH) The Government has certain rights in the invention.FIELD OF INVENTIONThis invention relates to novel compositions and methods of treatment of bacterial infections. Specifically, the invention provides novel peptidomimetic compounds, specifically novel sulfonyl-y-AApeptides that can be used for treating broad spectrum bacterial infections including those caused by drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).BACKGROUND OF THE INVENTIONAntimicrobial resistance (AMR) represents a critical and escalating threat global public health, progressively undermining the efficacy of conventional antimicrobial therapies11 2This challenge has been further exacerbated by the COVID-19 pandemic since 2019, which has facilitated the heightened transmission of resistant pathogens within overstretched healthcare systems3 4. As a result, AMR-attributable mortality has risen sharply, exceeding previous projections and is now estimated to reach up to 10 million deaths annually by 20505. Of particular concern are clinically significant multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA)6 7, methicillin-resistant Staphylococcus epidermidis (MRSE), and vancomycin-resistant Enterococcus faecium (VREF), which are major contributors to hospital-acquired infections characterized by limited therapeutic options and elevated mortality rates8. Collectively, the rapid dissemination of antibiotic resistance, driven by diverse and evolving molecular mechanisms9’10 11, ihas intensified global efforts to develop next-generation antimicrobial strategies with a reduced likelihood of resistance development12As central components of the innate immune system, naturally occurring antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), exhibited various biological activities, including direct antimicrobial action against bacteria, fungi, viruses and parasites, as well as immunomodulatory, wound-healing and antiinflammatory functions13. Among their vast diversity, the most prevalent AMPs are a-helical peptides, such as magainin 214and melittin15(Fig. 1A, B), which possess cationic and amphipathic characteristics that promote electronic interactions with negatively charged bacterial phopholipids16. These interactions induce membrane disruption, leakage of intracellular contents and subsequent cell death17, thereby reducing the risk of bacterial resistance developmentInspired by these natural templates, the synthetic AMP LL-3718(Fig. 1C) was developed and exhibits broad-spectrum activity. However, the clinical translation of natural AMPs remains limited by intrinsic challenges, including susceptibility to proteolytic degradation, potential cytotoxicity, limited target specificity, and high production costs. Consequently, substantial efforts have been devoted to the development of AMP-mimetic antimicrobial agents that recapitulate the structural and amphiphilic features of natural peptides19. Notably, antimicrobial compounds based on a / p amino acids, stapled peptides, peptoids20’21, and oligomers have demonstrated potent activities, significantly expanding the landscape of nextgeneration antimicrobial therapeutics.A unique class of peptidomimetics called sulfonyl-y-AApeptide foldamers have been previously developed and characterized by their rigid helical secondary structures which are distinguished by their enhanced structural diversity and synthetic accessibility. They have been shown to have improved stability, favorable pharmacokinetics, and promising application in biomedicine and material science. However, sulfonyl-y-AApeptides have not been examined for treatment of drugresistant bacterial infections, such as MRSA.Accordingly, what is needed is an improved therapeutic agent with broad applications for addressing a variety of unmet medical needs, including drug-resistant bacterial infections. However, in view of the art considered as a whole at the time the present invention was made, it was not obvious to those of ordinary skill in the field of this invention how the shortcomings of the prior art could be overcome.SUMMARY OF INVENTIONIn an aspect, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, is disclosed comprising:wherein R1 is independently selected fromwherein R2 is independently selected from; andwherein n is an integer from 1 to 8.In certain aspects, n is 8.In a certain aspects, the compound is AMD-1 , or a pharmaceutically acceptable salt thereof, comprising Formula (II):(II).In a certain aspects, the compound is AMD-2, or a pharmaceutically acceptable salt thereof, comprising Formula (III):(III).In a certain aspects, the compound is AMD-3, or a pharmaceutically acceptable salt thereof, comprising Formula (IV):In a certain aspects, the compound is AMD-4, or a pharmaceutically acceptable salt thereof, comprising Formula (V):"In a certain aspects, the compound is AMD-5, or a pharmaceutically acceptable salt thereof, comprising Formula (VI):In a certain aspects, the compound is AMD-6, or a pharmaceutically acceptable salt thereof, comprising Formula (VII):In a certain aspects, the compound is AMD-7, or a pharmaceutically acceptable salt thereof, comprising Formula (VIII):(VIII).In a certain aspects, the compound is AMD-8, or a pharmaceutically acceptable salt thereof, comprising Formula (IX):(IX).In a certain aspects, the compound is AMD-9, or a pharmaceutically acceptable salt thereof, comprising Formula (X):In a certain aspects, the compound is AMD-10, or a pharmaceutically acceptable salt thereof, comprising Formula (XI):(XI).In a certain aspects, the compound is AMD-11 , or a pharmaceutically acceptable salt thereof, comprising Formula (XII):In a certain aspects, the compound is AMD-12, or a pharmaceutically acceptable salt thereof, comprising Formula (XIII):(XIII).In a certain aspects, the compound is AMD-13, or a pharmaceutically acceptable salt thereof, comprising Formula (XIV):In a certain aspects, the compound is AMD-14, or a pharmaceutically acceptable salt thereof, comprising Formula (XV):In a certain aspects, the compound is AMD-15, or a pharmaceutically acceptable salt thereof, comprising Formula (XVI):(XVI).In a certain aspects, a compound of Formula (XVII), or a pharmaceutically acceptable salt thereof, is disclosed comprising:< < < &""" " (XVII);wherein R1 is independently selected from, orIn an aspect, disclosed herein is a pharmaceutical composition comprising a compound of Formula (I-XVII), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.In an aspect, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) inhibits both Gram positive and Gram negative bacteria, including drug-resistant bacteria.In certain aspects, the compound of Formula (I-XVII), or a pharmaceutical salt thereof, exhibits bactericidal and / or bacteriostatic effects on the bacterial infection to treat the antibacterial infection.In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof.In an aspect, the bacteria is a Gram positive (Gram (+)) bacteria. Non-limiting examples of Gram positive bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, and / or Streptococcus pneumoniaeIn an aspect, the bacteria is a Gram negative (Gram (-)) bacteria. Non-limiting examples of Gram negative bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterlum granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratiamarcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, and / or Yersinia enterocolitica.In an aspect, the bacteria is a drug-resistant bacteria Non-limiting examples of drugresistant bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of inducing bacteria death is disclosed, the method comprising contacting the bacteria with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) induces bacteria death in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In an aspect, the bacteria comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetanl, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia fells, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus Influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistantStaphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epldermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of reducing bacteria proliferation is disclosed, the method comprising contacting the bacteria with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) reduces bacteria proliferation in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In an aspect, the bacteria comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii(CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of inhibiting biofilm formation in a bacterial infection in a patient in need thereof is disclosed, the method comprising administering to the patient a therapeutically effective amount of compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier wherein the therapeutically effective amount of the compound or the pharmaceutical composition inhibits biofilm formation. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) inhibits biofilm formation both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof.In an aspect, the bacteria is a Gram positive (Gram +) bacteria. Non-limiting examples of Gram + bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, and / or Streptococcus pneumoniae.In an aspect, the bacteria is a Gram negative (Gram -) bacteria. Non-limiting examples of Gram - bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Afipia felis, Bacteriodes, Bartonella bacllliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, and / or Yersinia enterocolitica.In an aspect, the bacteria is a drug-resistant bacteria. Non-limiting examples of drugresistant bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of increasing membrane permeability in a bacterium is disclosed, the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) increases bacterial membrane permeability in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In an aspect, the bacterium comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia fells, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis(MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilias influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of inducing membrane depolarization in a bacterium is disclosed, the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) induces membrane depolarization both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In an aspect, the bacterium comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptibleStreptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of inducing membrane disruption in a bacterium is presented, the method comprising the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) induces membrane disruption in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In an aspect, the bacterium comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of inducing ROS accumulation in a bacterium is disclosed, the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) induces ROS accumulation in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In an aspect, the bacterium comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a kit is disclosed, the kit comprising a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; and instructions for use.BRIEF DESCRIPTION OF THE DRAWINGSFor a fuller understanding of the invention, reference should be made to the following detailed description, taken in connection with the accompanying drawings, in which:FIG. 1 A-E are a series of images depicting representative a-helical natural, synthetic AMPs and sulfonyl-y-AApeptides with antimicrobial activity. (A) Ribbon and surface view of magainin 2 (PDB: 9HVN), (B) melittin (PDB: 6O4M), (C) LL-37 (PDB: 6S6N), (D) sulfonyl-y-AApeptide AM10. Hydrophobic, cationic, hydrophilic and anionic residues are represented. (E) mechanism of action of AM10.FIG. 2A-F is a series of images depicting structure of D-sulfonyl-y-AApeptides. (A) Chemical structure sulfonyl-y-AApeptide. (B) Structural template of 8-mer antimicrobial sulfonyl-y-AApeptide: a, b represents chiral and achiral side chains.(C,D) Crystal structure of sulfonyl-y-AApeptide: (C) side view, (D) top view. (E,F) Schematic representation of side-chains distribution in helical scaffold: (E) side view, (F) top view..FIG. 3 is a table depicting Structures of antimicrobial sulfonyl-y-AApeptides.FIG. 4A-B are a series of images depicting time-kill kinetics and drug resistance development of AM 10. (A) Time-kill kinetic curve of AM10 against E. coli and (B) MRSA FIG. 4C-D are a series of images depicting drug resistance development of AM10 against (C) E. coli and (D) MRSA.FIG. 5 is an image depicting biomass remaining of E. coli and MRSA after treatment of AM 10.FIG.6A-B are a series of graphs depicting membrane permeability and depolarization tests of AM10 (A) Outer membrane permeability of E coli using NPN and (B) Inner membrane of E. coli with treatment of AM10 using ONPG.FIG. 6C-D are a series of graphs depicting membrane depolarization of (C) E coli and (D) MRSA with DiSC3(5).FIG. 7A is a series of images depicting microscopic studies of AM10 (A) T ransmission electron microscopy (TEM) image of MRSA and E. coli before and after treatment of AM10 for 2h.FIG. 7B is a series of images depicting microscopic studies of AM10. (B) Fluorescence imaging of E. coli and MRSA untreated and treated with AM10.FIG.8A-B are a series of graphs depicting excessive reactive oxygen species (ROS) accumulation induced by AM 10. Accumulation of ROS overtime in (A) E. coli and (B) MRSA FIG.8C-D are a series of graphs depicting Inhibition of dehydrogenase activity of (C) E. coll and (D) MRSA.FIG.9A-C is a series of images depicting cytotoxicity and in vivo activity of AM10. (A) Cell viability of HeLa cells with AM 10 treatment. (B) Schematic diagram of in vivo activity study using thigh burden mice model. (C) Bacterial load in thigh after treatment with PBS, ciprofloxacin and AM10, respectively. ****P<0.0001.DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTIn the following detailed description of the preferred embodiments, reference is made to the accompanying drawings, which form a part hereof, and within which are shown by way of illustration specific embodiments by which the invention may be practiced. It is to be understood that other embodiments may be utilized, and structural changes may be made without departing from the scope of the invention.DefinitionsUnless otherwise defined, 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, some potential and preferred methods and materials are described herein. All publications mentioned herein are incorporated herein by reference in their entirety to disclose and describe the methods and / or materials in connection with which the publications are cited. It is understood that the present disclosure supersedes any disclosure of an incorporated publication to the extent there is a contradiction. As used herein, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise.As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and / or” unless the context clearly dictates otherwise.All numerical designations, such as pH, temperature, time, concentration, and molecular weight, including ranges, are approximations which are varied up ordown by increments of 1.0, 0.1, 0.01 or 0.001 as appropriate. It is to be understood, even if it is not always explicitly stated that all numerical designations are preceded by the term “about.” It is also to be understood, even if it is not always explicitly stated, that the reagents described herein are merely exemplary and that equivalents of such are known in the art and can be substituted for the reagents explicitly stated herein. Concentrations, amounts, solubilities, and other numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. As an illustration, a numerical range of “about 1 to about 5” should be interpreted to include not only the explicitly recited values of about 1 to about 5 but also include the individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3, and 4 and sub-ranges such as from 1-3, from 2-4 and from 3-5, etc. This same principle applies to ranges reciting only one numerical value. Furthermore, such an interpretation should apply regardless of the range or the characteristics being describedAs used herein, the term “comprising” is intended to mean that the products, compositions, and methods include the referenced components or steps, but not excluding others. “Consisting essentially of when used to define products, compositions, and methods, shall mean excluding other components or steps of any essential significance that affect the novel characteristics of the invention as described herein. Thus, a composition consisting essentially of the recited components would not exclude trace contaminants and pharmaceutically acceptable carriers. “Consisting of” shall mean excluding more than trace elements of other components or steps.As used herein, “about” means approximately or nearly and in the context of a numerical value or range set forth means ±10% of the numerical.As used herein “patient” is used to describe a mammal, preferably a human, to whom treatment is administered, including prophylactic treatment with the compositions of the present invention. Non-limiting examples of mammals include humans, rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such assheep, pigs, cows, and horses. “Patient” and “subject” are used interchangeably herein.“Administering” or “administration” as used herein refers to the process by which the compositions of the present invention are delivered to the patient. The compositions may be administered in various ways, including but not limited to, orally, rectally, ocularly, mucosally, otically, inhalation, percutaneously, subcutaneously, topically, and parenterally, although other enteral and parenteral routes are contemplated. Any of the compounds may also be delivered through encapsulation in vesicles such as liposomes, niosomes, micelles, etc.“Parenteral administration” as used herein refers to modes of administration other than enteral and topical administration, usually by injection, and includes, but is not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, subcapsular, intrathecal, intraventricular, intracisternal, intranigral, subarachnoid, intraspinal, and intrasternal injection and infusion. Dosing can be by any suitable route, e.g., by injections, such as intravenous or percutaneous injections, depending in part on whether the administration is brief or chronic. Various dosing schedules including but not limited to, single or multiple administrations over various time-points, bolus administration, and pulse infusion are contemplated herein. The terms “reduce or inhibit” as used herein refers to the ability to cause an overall decrease of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or greater. Reduce or inhibit can refer, for example, to the symptoms of the disease being treated, to the amount of damage or injury incurred by the patient from the disease being treated, to the amount of bacteria proliferation, to the formation of biofilm produced by bacterial cells, to the incidence of drug-resistance development, etc.The terms “induce or enhance” as used herein refers to the ability to cause an overall increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or greater Induce or enhance can refer, for example, to bacterial cell death, to the disruption or rupture of the bacterial cell membrane, to depolarization of the bacterial cell membrane, to bacterial cell respiratory chain dysfunction, to reactive oxygen species (ROS) accumulation in bacterial cells, etc.A “therapeutic agent” or “pharmaceutically active agent” as used herein refers to a substance, composition, compound, chemical, component, or extract that hasmeasurable specified or selective physiological activity when administered to an individual in a therapeutically effective amount. In certain aspects, the therapeutic agent may be a peptide. In certain aspects, the therapeutic agent may be a small molecule. Examples of therapeutic agents capable of being used in the present invention include, but are not limited to, peptidomimetics such as sulfano-y-AApeptides. Non-limiting examples of sulfano-y-AApeptides useful herein include, but are not limited to, the compounds shown in Figure 3. At least one therapeutic agent is used in the compositions of the present invention, however in some embodiments, multiple therapeutic agents are used. In certain aspects, the therapeutic agents described herein may be combined with another therapeutic agent that targets a different disease target In certain aspects, one or more therapeutic agents may be encapsulated within a carrier vesicle such as a nanoparticle or micelle or other lipid carrier. In certain aspects, the therapeutic agent is used to treat an antimicrobial infection. In certain aspects, the antimicrobial infection is a bacterial infection. In certain aspects, the bacterial infection is drug-resistant.A “therapeutically effective amount” as used herein is defined as concentrations or amounts of components which are sufficient to effect beneficial or desired clinical results, including, but not limited to, any one or more of treating a microbial infection, particularly a bacterial infection. Compositions of the present invention can be used to effect a favorable change in the condition whether that change is an improvement, such as stopping, reversing, or a complete elimination of symptoms due to the disorder. In accordance with the present invention, a suitable single dose size is a dose that is capable of preventing or alleviating (reducing or eliminating) a symptom in a patient when administered one or more times over a suitable time period. One of skill in the art can readily determine appropriate single dose sizes for systemic administration based on the size of the animal and the route of administration. The dose may be adjusted according to response. In certain aspects, the therapeutic agent has a concentration of between about 1 pg / mLto about 150 pg / mL, preferably about 3 pg / mLto about 100 pg / mL, more preferably about 3 pg / mLto about 50 pg / mL, including all intervening values to the tenth of the numerical. In certain aspects, a therapeutically effective amount of a compound of the present disclosure may be about 1 mg / kg to about 1000 mg / kg, about 5 mg / kg to about 950 mg / kg, about 10 mg / kg to about 900 mg / kg, about 15 mg / kg to about 850 mg / kg, about 20 mg / kg to about 800 mg / kg, about 25 mg / kg to about 750 mg / kg, about 30 mg / kg to about 700 mg / kg, about 35 mg / kg to about 650 mg / kg, about 40 mg / kg to about 600 mg / kg, about 45 mg / kg to about 550 mg / kg, about 50 mg / kg to about 500 mg / kg, about 55 mg / kg to about 450 mg / kg, about 60 mg / kg to about 400 mg / kg, about 65 mg / kg toabout 350 mg / kg, about 70 mg / kg to about 300 mg / kg, about 75 mg / kg to about 250 mg / kg, about 80 mg / kg to about 200 mg / kg, about 85 mg / kg to about 150 mg / kg, and about 90 mg / kg to about 100 mg / kg. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, AMD-10 may be administered at a dose of 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35 mg / kg, 36 mg / kg, 37mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, or 50 mg / kg, including all intervening values to the tenth of the numerical.The dosing of compounds and compositions to obtain a therapeutic or prophylactic effect is determined by the circumstances of the patient, as is known in the art. The dosing of a patient herein may be accomplished through individual or unit doses of the compounds or compositions herein or by a combined or prepackaged or preformulated dose of a compounds or compositions.The amount of the therapeutic agent in the therapeutic composition will depend on absorption, distribution, metabolism, and excretion rates of the drug as well as other factors known to those of skill in the art. Dosage values may also vary with the severity of the condition to be alleviated. The therapeutic composition may be administered once or may be divided and administered over intervals of time. It is to be understood that administration may be adjusted according to individual need and professional judgment of a person administrating or supervising the administration of the compounds used in the present invention.The dose of the compounds administered to a subject may vary with the particular composition, the method of administration, and the particular disorder being treated. The dose should be sufficient to affect a desirable response, such as a therapeutic or prophylactic response against a particular disorder or condition. It is contemplated that one of ordinary skill in the art can determine and administer the appropriate dosage of compounds disclosed in the current invention according to the foregoing considerations.Dosing frequency for the composition includes, but is not limited to, at least about once every three weeks, once every two weeks, once a week, twice a week, threetimes a week, four times a week, five times a week, six times a week, or daily. In some embodiments, the interval between each administration is less than about a week, such as less than about any of 6, 5, 4, 3, 2, or 1 day. In some embodiments, the interval between each administration is constant. For example, the administration can be carried out daily, every two days, every three days, every four days, every five days, or weekly. In some embodiments, the administration can be carried out twice daily, three times daily, or more frequently. Administration can also be continuous and adjusted to maintaining a level of the compound within any desired and specified range. In certain aspects, the therapeutically effective dose is administered once per week.The administration of the composition can be extended over an extended period of time, such as from about a week or shorter up to about a year or longer. For example, the dosing regimen can be extended over a period of any of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 months. In some embodiments, there is no break in the dosing schedule. In some embodiments, the interval between each administration is no more than about a week.The therapeutic agents used in the present invention may be administered individually, or in combination with or concurrently with one or more other therapeutic agents used against autoimmune disorders. Additionally, therapeutic agents used in the present invention may be administered in combination with or concurrently with other therapeutics for bacterial infections.“Treatment” or “treating” as used herein refers to any of the alleviation, amelioration, elimination, and / or stabilization of a symptom, as well as delay in progression of a symptom of a particular disease or disorder, particularly bacterial infections. For example, “treatment” of a bacterial infection may include any one or more of the following: amelioration and / or elimination of one or more symptoms associated with a bacterial infection, reduction of one or more symptoms of a bacterial infection, stabilization of symptoms of a bacterial infection, and delay in progression of one or more symptoms of a bacterial infection.The pharmaceutical compositions of the instant invention may comprise sufficient material to produce a therapeutically effective amount of the compound of interest, i.e , an amount sufficient to reduce or ameliorate symptoms of the bacterial infection, or an amount sufficient to confer the desired benefit. The pharmaceutical compositions of the subject invention can be formulated according to known methods for preparing pharmaceutically useful compositions. When the therapeutic agents ofthe 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. Furthermore, as used herein, the phrase “pharmaceutically acceptable carrier” means any of the standard pharmaceutically acceptable carriers. The pharmaceutically acceptable carrier can include excipients, diluents, adjuvants, and vehicles, as well as implant carriers, and inert, non-toxic solid or liquid fillers, diluents, or encapsulating material that does not react with the active ingredients of the invention and do not themselves induce the production of antibodies harmful to the individual receiving the composition, and which may be administered without undue toxicity. Examples include, but are not limited to, phosphate buffered saline, physiological saline, water, and emulsions, such as oil / water emulsions. The carrier can be a solvent or dispersing medium containing, for example, ethanol, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. Example of suitable excipients include, but are not limited to, sorbitol, Tween80, and liquids such as water, saline, glycerol, and ethanol. Pharmaceutically acceptable salts can be included therein, for example, mineral acid salts such as hydrochlorides, hydrobromides, phosphates, sulfates, and the like; and the salts of organic acids such as acetates, propionates, malonates, benzoates, and the like. Additionally, auxiliary substances, such as wetting or emulsifying agents, pH buffering substances, and the like, may be present in such vehicles. Formulations are described in a number of sources that are well known and readily available to those skilled in the art. For example, Remington’s Pharmaceutical Sciences (Martin EW

[1995] Easton Pennsylvania, Mack Publishing Company, 19thed.) describes formulations which can be used in connection with the subject invention.For ease of administration, the subject compounds may be formulated into various pharmaceutical forms. As appropriate compositions there may be cited all compositions usually employed for systemically or topically administering drugs To prepare the pharmaceutical compositions of this invention, a therapeutically effective amount of a peptidomimetic such as a sulfano-y-AApeptide as described herein, as the active ingredient, is combined in intimate admixture with a pharmaceutically acceptable carrier, which may take a wide variety of forms depending on the form of preparation desired for administration. These pharmaceutical compositions are desirably in unitary dosage form suitable, preferably, for administration mucosally, nasally, orally, percutaneously, subcutaneously, topically, or by parenteral injection. For example, in preparing the compositions in oral dosage form, any of the usualpharmaceutical media may be employed, such as, for example, water, glycols, oils, alcohols and the like in the case of oral liquid preparations such as suspensions, syrups, elixirs and solutions; or solid carriers such as starches, sugars, kaolin, lubricants, binders, disintegrating agents and the like in the case of powders, pills, capsules and tablets. Because of their ease in administration, tablets and capsules often represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. For parenteral compositions, the carrier will usually comprise sterile water, at least in large part, though other ingredients, for example, to aid solubility, may be included Injectable solutions, for example, may be prepared in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution.“Building block” or “scaffold” as used herein refers to a common chemical structure characterizing a group of molecules. In some embodiments, the building block is a sulfano-y-AA peptide scaffold having the structure of Formula (I).The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopically enriched variants of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified. When the compound name disclosed herein conflicts with the structure depicted, the structure shown will supersede the use of the name to define the compound intended.As used herein, the term “substituent” means positional variables on the atoms of a core molecule that are attached at a designated atom position, replacing one or more hydrogen atoms on the designated atom, provided that the atom of attachment does not exceed the available valence or shared valence, such that the substitution results in a stable compound. Accordingly, combinations of substituents and / or variables are permissible only if such combinations result in stable compounds Any carbon atom as well as heteroatom with a valence level that appears to be unsatisfied as described or shown herein is assumed to have a sufficient number of hydrogen atom(s) to satisfy the valences described or shown.For the purposes of this description, where one or more substituent variables for a compound of Formula (I) encompass functionalities incorporated into a compound of Formula (I), each functionality appearing at any location within the disclosed compound may be independently selected, and as appropriate, independently and / or optionally substituted.As used herein, the terms “independently selected,” or “each selected” refer to functional variables in a substituent list that may be attached more than once on the structure of a core molecule, where the pattern of substitution at each occurrence is independent of the pattern at any other occurrence Further, the use of a generic substituent variable on a core structure for a compound described herein is understood to include the replacement of the generic substituent with species substituents that are included within the particular genus, e g., aryl may be replaced with phenyl or naphthalenyl and the like, such that the resulting compound is to be included within the scope of the compounds described hereinAs used herein, the term “optionally substituted” means that the specified substituent variables, groups, radicals or moieties represent the scope of the genus and may be independently chosen as needed to replace one or more hydrogen atoms on the designated atom of attachment of a core molecule.As used herein, the terms “stable compound” or “stable structure” mean a compound that is sufficiently robust to be isolated to a useful degree of purity from a reaction mixture and formulations thereof into an efficacious therapeutic agent.As used herein, the term “form” means a compound of Formulas (l-XVI) selected from a free acid, free base, salt, ester, hydrate, solvate, chelate, clathrate, polymorph, isotopologue, stereoisomer, racemate, enantiomer, diastereomer, or tautomer thereof.As used herein, the term “prodrug” means that a functional group on a compound of Formulas (I-XVII) is in a form (e.g., acting as an active or inactive drug precursor) that is transformed in vivo to yield an active or more active compound of Formulas (I- XVII) or a form thereof. The transformation may occur by various mechanisms (e.g., by metabolic and / or non-metabolic chemical processes), such as, for example, by hydrolysis and / or metabolism in blood, liver and / or other organs and tissues. A discussion of the use of prodrugs is provided by V J. Stella, et. al., “Biotechnology: Pharmaceutical Aspects, Prodrugs: Challenges and Rewards,” American Association of Pharmaceutical Scientists and Springer Press, 2007.The compounds of Formulas (I-XVII) or a form thereof can form salts, which are intended to be included within the scope of this description. Reference to a compound of Formulas (I-XVII) or a form thereof herein is understood to include reference to salts thereof, unless otherwise indicated. The term “salt(s)”, as employed herein,denotes acidic salts formed with inorganic and / or organic acids, as well as basic salts formed with inorganic and / or organic bases.The term “pharmaceutically acceptable salt(s)”, as used herein, means those salts of compounds of Formulas (l-XVI I ) or a form thereof described herein that are safe and effective (i.e., non-toxic, physiologically acceptable) for use in mammals and that possess biological activity, although other salts are also useful. All such acid salts and base salts are intended to be included within the scope of pharmaceutically acceptable salts as described herein. In addition, all such acid and base salts are considered equivalent to the free forms of the corresponding compounds for purposes of this description.The use of the terms “salt,” “solvate,” “ester,” “prodrug” and the like, is intended to apply equally to the salt, solvate, ester and prodrug of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates, isotopologues or prodrugs of the instant compounds.Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e g., enantiomeric, diastereomeric, optical, and geometric (or conformational)) forms of the structure or a form thereof (including salts, solvates, esters, and prodrugs and transformed prodrugs thereof); for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms.The compounds of Formulas (I-XVII) or a form thereof described herein may include one or more chiral centers, and as such may exist as racemic mixtures (R / S) or as substantially pure enantiomers and diastereomers The compounds may also exist as substantially pure (R) or (S) enantiomers (when one chiral center is present). In one embodiment, the compounds of Formulas (I-XVII) or a form thereof described herein are (S) isomers and may exist as enantiomerically pure compositions substantially comprising only the (S) isomer. In another embodiment, the compounds of Formulas (I-XVII) or a form thereof described herein are (R) isomers and may exist as enantiomerically pure compositions substantially comprising only the (R) isomer.As one of skill in the art will recognize, when more than one chiral center is present, the compounds of Formulas (l-XVIl) or a form thereof described herein may also exist as a (R,R), (R,S), (S,R) or (S,S) isomer, as defined by IUPAC Nomenclature Recommendations.As used herein, the term “substantially pure” refers to compounds of Formulas (I-XVII) or a form thereof consisting substantially of a single isomer in an amount greater than or equal to 90%, in an amount greater than or equal to 92%, in an amount greater than or equal to 95%, in an amount greater than or equal to 98%, in an amount greater than or equal to 99%, or in an amount equal to 100% of the single isomer.As used herein, the term “racemate” refers to any mixture of isometric forms that are not “enantiomerically pure”, including mixtures such as, without limitation, in a ratio of about 50 / 50, about 60 / 40, about 70 / 30, or about 80 / 20, about 85 / 15 or about 90 / 10. All stereoisomers (for example, geometric isomers, optical isomers and the like) of the present compounds of Formulas (l-XVIl) or a form thereof (including salts, solvates, esters and prodrugs and transformed prodrugs thereof), which may exist due to asymmetric carbons on various substituents, including enantiomeric forms (which may exist even in the absence of asymmetric carbons), rotameric forms, atropisomers, diastereomeric and regioisomeric forms, are contemplated within the scope of the description herein. Individual stereoisomers of the compounds of Formulas (l-XVIl) or a form thereof described herein may, for example, be substantially free of other isomers, or may be present in a racemic mixture, as described supra.The term “isotopologue” refers to isotopically-enriched compounds of Formulas (I-XVII) or a form thereof which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature.One or more compounds of Formulas (l-XVIl) or a form thereof described herein may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and the description herein is intended to embrace both solvated and unsolvated formsAs used herein, the term “solvate” means a physical association of a compound of Formulas (l-XVIl) or a form thereof described herein with one or more solvent molecules. This physical association involves varying degrees of ionic and covalentbonding, including hydrogen bonding. In certain instances, the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. As used herein, “solvate” encompasses both solution-phase and isolatable solvatesPolymorphic crystalline and amorphous forms of the compounds of Formulas (I-XVII) or a form thereof, and of the salts, solvates, esters and prodrugs of the compounds of Formulas (I-XVII) or a form thereof, are further intended to be included in the scope of the compounds of Formulas (I-XVII) or a form thereof described herein.Also falling within the scope described herein are the in vivo metabolic products of the compounds of Formulas (I-XVII) or a form thereof. Such products may result, for example, from the oxidation, reduction, hydrolysis, amidation, glucuronidation, esterification and the like of the administered compound of Formulas (I- XVII) or a form thereof, primarily due to enzymatic processes. Accordingly, the compounds of Formulas (I-XVII) or a form thereof described herein include those produced by a process comprising contacting a compound of Formulas (I-XVII) or a form thereof described herein with a mammalian tissue or a mammal for a period of time sufficient to yield a metabolic product thereof.“Infection” as used herein refers to the invasion of one or more microorganisms such as bacteria, viruses, fungi, yeast or parasites in the body of a patient in which they are not normally present. In certain aspects, the infection is a bacterial infection. “Antimicrobial” as used herein refers to synthetic compositions capable of killing or inhibiting the growth of microorganisms including, but not limited to, bacteria, fungi, viruses, protozoa and parasites. Antimicrobials used herein include antibiotics, antivirals, antifungals, antiprotozoals, and antiparasitics. In certain aspects, the antimicrobial is an antibiotic. In certain aspects, the antibiotic is a peptidomimetic, preferably a sulfonyl-y-AApeptide.“Bacteria” as used herein refers to microorganisms in the bacteria domain and bacterial spores and / or vegetative bacteria. The term “bacteria” or “bacterium” are used interchangeably with “bacterial cell" herein. Bacteria include, but are not limited to, acid-fast bacteria, gram positive bacteria, and gram negative bacteria. Exemplary acid-fast bacteria include Myobacterium tuberculosis, Myobacterium avium, Myobacterium leprae, Mycobacterium ulcerans. Gram positive bacteria include, but are not limited to, Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens,Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, and Streptococcus pneumoniae. Gram negative bacteria include, but are not limited to, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, and Yersinia. Other bacteria not falling into the other three categories include, but are not limited to, Bartonella henseiae, Chlamydia psittaci, Chlamydia trachomatis, Coxiella burnetii, Mycoplasma pneumoniae, Rickettsia akari, Rickettsia prowazekii, Rickettsia rickettsii, Rickettsia tsutsugamushi, Rickettsia typhi, Ureaplasma urealyticum, Diplococcus pneumoniae, Ehrlichia chafensis, Enterococcus faecium, and Meningococci.“Drug-resistant bacteria” as used herein refers to bacteria which are impervious to the effects of one or more classes of antibiotics. Non-limiting examples of drugresistant bacteria include, but are not limited to, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and rifampicin-resistant Mycobacterium tuberculosis.“Biofilm” as used herein refers to a layer of microorganisms, encased in a matrix, which forms on a biotic or abiotic surface. In many cases, the biofilm is formed from a community of bacteria enclosed in an exopolysaccharide matrix. The biofilm may be monomicrobial or polymicrobial.CompoundsIn an aspect, a compound of Formula (I), or a pharmaceutically acceptable salt thereof, is disclosed comprising:(i);wherein R1 is independently selected fromwherein R2 is independently selected fromwherein n is an integer from 1 to 8.In certain aspects, n is 8.In a certain aspects, the compound is AMD-1 , or a pharmaceutically acceptable salt thereof, comprising Formula (II):(II).In a certain aspects, the compound is AMD-2, or a pharmaceutically acceptable salt thereof, comprising Formula (III):(III).In a certain aspects, the compound is AMD-3, or a pharmaceutically acceptable salt thereof, comprising Formula (IV):In a certain aspects, the compound is AMD-4, or a pharmaceutically acceptable salt thereof, comprising Formula (V):"In a certain aspects, the compound is AMD-5, or a pharmaceutically acceptable salt thereof, comprising Formula (VI):In a certain aspects, the compound is AMD-6, or a pharmaceutically acceptable salt thereof, comprising Formula (VII):In a certain aspects, the compound is AMD-7, or a pharmaceutically acceptable salt thereof, comprising Formula (VIII):(VIII).In a certain aspects, the compound is AMD-8, or a pharmaceutically acceptable salt thereof, comprising Formula (IX):(IX).In a certain aspects, the compound is AMD-9, or a pharmaceutically acceptable salt thereof, comprising Formula (X):In a certain aspects, the compound is AMD-10, or a pharmaceutically acceptable salt thereof, comprising Formula (XI):(XI).In a certain aspects, the compound is AMD-11 , or a pharmaceutically acceptable salt thereof, comprising Formula (XII):In a certain aspects, the compound is AMD-12, or a pharmaceutically acceptable salt thereof, comprising Formula (XIII):(XIII).In a certain aspects, the compound is AMD-13, or a pharmaceutically acceptable salt thereof, comprising Formula (XIV):(XIV).In a certain aspects, the compound is AMD-14, or a pharmaceutically acceptable salt thereof, comprising Formula (XV):In a certain aspects, the compound is AMD-15, or a pharmaceutically acceptable salt thereof, comprising Formula (XVI):(XVI).In a certain aspects, a compound of Formula (XVII), or a pharmaceutically acceptable salt thereof, is disclosed comprising:< &(XVII);wherein R1 is independently selected fromor; andwherein R2 is independently selected fromPharmaceutical CompositionsThe compounds disclosed herein may be incorporated into pharmaceutical compositions suitable for administration to a subject (such as a human or non-human subject). For example, disclosed herein is a pharmaceutical composition comprising a compound of Formula (I-XVII), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof.The pharmaceutical composition may include a therapeutically effective amount of the therapeutic agent (compound) which refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result. A therapeutically effective amount is also one in which any toxic or detrimental effects of a compound of the disclosure are outweighed by the therapeutically beneficial effects.For example, a therapeutically effective amount of a compound of the present disclosure, may be about 1 mg / kg to about 1000 mg / kg, about 5 mg / kg to about 950 mg / kg, about 10 mg / kg to about 900 mg / kg, about 15 mg / kg to about 850 mg / kg, about 20 mg / kg to about 800 mg / kg, about 25 mg / kg to about 750 mg / kg, about 30 mg / kg to about 700 mg / kg, about 35 mg / kg to about 650 mg / kg, about 40 mg / kg to about 600 mg / kg, about 45 mg / kg to about 550 mg / kg, about 50 mg / kg to about 500 mg / kg, about 55 mg / kg to about 450 mg / kg, about 60 mg / kg to about 400 mg / kg, about 65 mg / kg to about 350 mg / kg, about 70 mg / kg to about 300 mg / kg, about 75 mg / kg to about 250 mg / kg, about 80 mg / kg to about 200 mg / kg, about 85 mg / kg to about 150 mg / kg, and about 90 mg / kg to about 100 mg / kg.In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical.As defined previously, the pharmaceutical compositions may include pharmaceutically acceptable carriers which are non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as, but not limited to, lactose, glucose and sucrose; starches such as, but not limited to, corn starch and potato starch; cellulose and its derivatives such as, but not limited to, sodium carboxymethyl cellulose, ethyl cellulose and celluloseacetate; powdered tragacanth; malt; gelatin; talc; excipients such as, but not limited to, cocoa butter and suppository waxes; oils such as, but not limited to, peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols such as propylene glycol; esters such as, but not limited to, ethyl oleate and ethyl laurate; agar; buffering agents such as, but not limited to, magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer’s solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as, but not limited to, sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator.As defined previously, the therapeutic agents (compounds) described herein or a pharmaceutical composition thereof can be administered to a patient in need thereof by any accepted route of administration including, but not limited to, orally, ocularly, otically, mucosally, percutaneously, subcutaneously, topically, and parenterally. In instances of parenteral administration, typically, such compositions can be prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for use to prepare solutions or suspensions upon the addition of a liquid prior to injection can also be prepared; and the preparations can also be emulsified. The preparation of such formulations will be known to those of skill in the art in light of the present disclosure.The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions; formulations including sesame oil, peanut oil, or aqueous propylene glycol; and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases the form must be sterile and must be fluid to the extent that it may be easily injected. It also should be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi.The carrier also can 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 can 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. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of theinjectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin. Sterile injectable solutions are prepared by incorporating the active compounds in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum-drying and freeze-drying techniques, which yield a powder of the active ingredient, plus any additional desired ingredient from a previously sterile-filtered solution thereof.In other aspects, the compounds described herein or a pharmaceutical composition thereof are suitable for local delivery to the digestive or Gl tract by way of oral administration (e.g., solid or liquid dosage forms.).Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the compound is mixed with one or more pharmaceutically acceptable excipients, such as sodium citrate or dicalcium phosphate and / or: a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.In certain aspects, the compositions will take the form of a unit dosage form such as a pill or tablet and thus the composition may contain, along with a compound provided herein, a diluent such as lactose, sucrose, dicalcium phosphate, or the like; alubricant such as magnesium stearate or the like; and a binder such as starch, gum acacia, polyvinylpyrrolidine, gelatin, cellulose, cellulose derivatives or the like. In another solid dosage form, a powder, marume, solution or suspension (e.g., in propylene carbonate, vegetable oils, PEG’S, poloxamer 124 or triglycerides) is encapsulated in a capsule (gelatin or cellulose base capsule). Unit dosage forms in which one or more compounds provided herein, or additional active agents are physically separated are also contemplated; e.g., capsules with granules (or tablets in a capsule) of each drug; two-layer tablets; two-compartment gel caps, etc. Enteric coated or delayed release oral dosage forms are also contemplated.Other physiologically acceptable compounds include wetting agents, emulsifying agents, dispersing agents or preservatives that are particularly useful for preventing the growth or action of microorganisms. Various preservatives are well known and include, for example, phenol and ascorbic acidIn certain aspects, the excipients are sterile and generally free of undesirable matter. These compositions can be sterilized by conventional, well-known sterilization techniques. For various oral dosage form excipients such as tablets and capsules sterility is not required. The USP / NF standard is usually sufficient.In certain aspects, solid oral dosage forms can further include one or more components that chemically and / or structurally predispose the composition for delivery of the chemical entity to the stomach or the lower Gl; e.g., the ascending colon and / or transverse colon and / or distal colon and / or small bowel. Exemplary formulation techniques are described in, e.g., Filipski, K.J., et al., Current Topics in Medicinal Chemistry, 2013, 13, 776-802, which is incorporated herein by reference in its entirety.Examples include upper-GI targeting techniques, e.g., Accordion Pill (Intec Pharma), floating capsules, and materials capable of adhering to mucosal walls.Other examples include lower-GI targeting techniques. For targeting various regions in the intestinal tract, several enteric / pH-responsive coatings and excipients are available. These materials are typically polymers that are designed to dissolve or erode at specific pH ranges, selected based upon the Gl region of desired drug release. These materials also function to protect acid labile drugs from gastric fluid or limit exposure in cases where the active ingredient may be irritating to the upper Gl (e.g., hydroxypropyl methylcellulose phthalate series, Coateric (polyvinyl acetate phthalate), cellulose acetate phthalate, hydroxypropyl methylcellulose acetatesuccinate, Eudragit series (methacrylic acid-methyl methacrylate copolymers), and Marcoat). Other techniques include dosage forms that respond to local flora in the Gl tract, Pressure-controlled colon delivery capsule, and Pulsincap.Ocular compositions can include, without limitation, one or more of any of the following: viscogens (e.g., Carboxymethylcellulose, Glycerin, Polyvinylpyrrolidone, Polyethylene glycol); Stabilizers (e.g., Pluronic (triblock copolymers), Cyclodextrins); Preservatives (e.g., Benzalkonium chloride, ETDA, SofZia (boric acid, propylene glycol, sorbitol, and zinc chloride; Alcon Laboratories, Inc.), Purite (stabilized oxychloro complex; Allergan, Inc.)).Topical compositions can include ointments, creams, gels, or liquids. Ointments are semisolid preparations that are typically based on petrolatum or other petroleum derivatives Creams containing the selected active agent are typically viscous liquid or semisolid emulsions, often either oil-in-water or water-in-oil. Cream bases are typically water-washable, and contain an oil phase, an emulsifier and an aqueous phase. The oil phase, also sometimes called the “internal” phase, is generally comprised of petrolatum and a fatty alcohol such as cetyl or stearyl alcohol; the aqueous phase usually, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant. The emulsifier in a cream formulation is generally a nonionic, anionic, cationic or amphoteric surfactant. As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and nonsensitizing. Gels containing the active agent are typically water-soluble semi-solids containing less oil than a cream.Methods of TreatmentIn an aspect, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (II) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (II) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (II) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (II) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (III) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (III) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (IV) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (IV) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (IV) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (IV) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (V) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (V) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (VI) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (VI) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (VII) or a pharmaceutically acceptable salt thereof,or a pharmaceutical composition comprising a compound of Formula (VII) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (VIII) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (VIII) or a pharmaceutically acceptable salt thereof.In certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (IX) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (IX) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (X) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (X) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (XI) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (XI) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (XII) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (XII) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (XIII) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (XIII) or a pharmaceutically acceptable salt thereof.In certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (XIV) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (XIV) or a pharmaceutically acceptable salt thereof.In certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (XV) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (XV) or a pharmaceutically acceptable salt thereofIn certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, comprising administering to the patient a therapeutically effective amount of a compound of Formula (XVI) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (XVI) or a pharmaceutically acceptable salt thereof.In certain aspects, a method of treating an antibacterial infection in a patient in need thereof is disclosed, the method comprising administering to the patient a therapeutically effective amount of a compound of Formula (XVII) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (XVII) or a pharmaceutically acceptable salt thereof.In certain aspects, the compound of Formula (I-XVII), or a pharmaceutical salt thereof, exhibits bactericidal and / or bacteriostatic effects on the bacterial infection to treat the antibacterial infection. In certain aspects, the minimum bactericidal activity of the compound is at least 1 pg / mL to about 150 pg / mL, about 3 pg / mL to about 120 pg / mL, about 3 pg / mL to about 70 pg / mL, including all intervening values to the tenth of the numerical. In certain aspects, a therapeutically effective amount of the compound of the present disclosure may be about 1 mg / kg to about 1000 mg / kg, about 5 mg / kg to about 950 mg / kg, about 10 mg / kg to about 900 mg / kg, about 15 mg / kg to about 850 mg / kg, about 20 mg / kg to about 800 mg / kg, about 25 mg / kg to about 750 mg / kg, about 30 mg / kg to about 700 mg / kg, about 35 mg / kg to about 650 mg / kg, about 40 mg / kg to about 600 mg / kg, about 45 mg / kg to about 550 mg / kg, about 50 mg / kg to about 500 mg / kg, about 55 mg / kg to about 450 mg / kg, about 60 mg / kg to about 400 mg / kg, about 65 mg / kg to about 350 mg / kg, about 70 mg / kg to about 300 mg / kg, about 75 mg / kg to about 250 mg / kg, about 80 mg / kg to about 200mg / kg, about 85 mg / kg to about 150 mg / kg, and about 90 mg / kg to about 100 mg / kg, including all intervening amounts to the tenth of the numerical.In certain aspects, the compound has a selective index for a given bacterium of at least 10 (e.g., at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 50, at least 60, at least 70, at least 75, at least 80, at least 85, at least 90, or at least 95)In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof.In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, the compound of Formula (l-XVIl) or composition comprising the compound of Formula (l-XVIl) inhibits both Gram positive and Gram negative bacteria, including drug-resistant bacteria.In an aspect, the bacteria is a Gram positive (Gram (+)) bacteria. Non-limiting examples of Gram positive bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, and / or Streptococcus pneumoniaeIn an aspect, the bacteria is a Gram negative (Gram (-)) bacteria. Non-limiting examples of Gram negative bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Afipia felis, Bacteriodes, Bartonella bacllliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratiamarcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, and / or Yersinia enterocolitica.In an aspect, the bacteria is a drug-resistant bacteria Non-limiting examples of drugresistant bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of inducing bacteria death is disclosed, the method comprising contacting the bacteria with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) induces bacteria death in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In an aspect, the bacteria comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetanl, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia fells, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus Influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistantStaphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epldermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis. In certain aspects, the contacting occurs in vivo. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, the contacting occurs in vitro.In an aspect, a method of reducing bacteria proliferation is disclosed, the method comprising contacting the bacteria with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (l-XVIl) or a pharmaceutical composition comprising a compound of Formula (l-XVIl) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (l-XVIl) or composition comprising the compound of Formula (l-XVIl) reduces bacteria proliferation in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In an aspect, the bacteria comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentls, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptlus, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epldermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridls, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilias influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis. In certain aspects, the contacting occurs in vivo. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, the contacting occurs in vitro.In an aspect, a method of inhibiting biofilm formation in a bacterial infection in a patient in need thereof is disclosed, the method comprising administering to the patient a therapeutically effective amount of compound, or pharmaceutically acceptable salt thereof, of Formula (l-XVIl) or a pharmaceutical composition comprising a compound of Formula (l-XVIl) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier wherein the therapeutically effective amount of the compound or the pharmaceutical composition inhibits biofilm formation. In certain aspects, the compound of Formula (l-XVIl) or composition comprising the compound of Formula (l-XVIl) inhibits biofilm formation of both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical.In an aspect, the bacteria is a Gram positive (Gram (+)) bacteria. Non-limiting examples of Gram (+) bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, and / or Streptococcus pneumoniaeIn an aspect, the bacteria is a Gram negative (Gram (-)) bacteria. Non-limiting examples of Gram (-) bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, and / or Yersinia enterocolitica.In an aspect, the bacteria is a drug-resistant bacteria. Non-limiting examples of drugresistant bacteria capable of being treated with the compounds and compositions disclosed herein include, but are not limited to, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.In an aspect, a method of increasing membrane permeability in a bacterium is disclosed, the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I-XVII) or a pharmaceutical composition comprising a compound of Formula (I-XVII) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In certain aspects, the compound of Formula (I-XVII) or composition comprising the compound of Formula (I-XVII) increases membrane permeability in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In an aspect, the bacterium comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani,Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis. In certain aspects, the contacting occurs in vivo. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, the contacting occurs in vitro.In an aspect, a method of inducing membrane depolarization in a bacterium is disclosed, the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (l-XVIl) or a pharmaceutical composition comprising a compound of Formula (l-XVIl) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (l-XVIl) or composition comprising the compound of Formula (l-XVIl) induces membrane depolarization in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In an aspect, the bacterium comprises Actlnomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani,Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis. In certain aspects, the contacting occurs in vivo. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, the contacting occurs in vitro.In an aspect, a method of inducing membrane disruption in a bacterium is presented, the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (l-XVIl) or a pharmaceutical composition comprising a compound of Formula (l-XVIl) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In certain aspects, the compound of Formula (l-XVIl) or composition comprising the compound of Formula (l-XVIl) induces membrane disruption in both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In an aspect, the bacterium comprises Actlnomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani,Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis. In certain aspects, the contacting occurs in vivo. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, the contacting occurs in vitro.In an aspect, a method of inducing ROS accumulation in a bacterium is disclosed, the method comprising contacting the bacterium with an effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (l-XVIl) or a pharmaceutical composition comprising a compound of Formula (l-XVIl) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In certain aspects, the compound of Formula (l-XVIl) or composition comprising the compound of Formula (l-XVIl) induces ROS accumulation both Gram positive and Gram negative bacteria, including drug-resistant bacteria. In certain preferred aspects, the compound is AMD-10 represented by Formula (XI), or a pharmaceutically acceptable salt thereof. In an aspect, the bacterium comprises Actlnomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani,Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coll, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinoloneresistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coll, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis. In certain aspects, the contacting occurs in vivo. In certain aspects, the therapeutic agent is AMD-10 administered at a therapeutically effective dose of between about 5 mg / kg to about 50 mg / kg, preferably about 10 mg / kg to about 30 mg / kg, including all intervening values to the tenth of the numerical. In certain aspects, the contacting occurs in vitro.KitsThe compounds disclosed herein may be included in kits comprising the compound, a systemic or topical composition, or both; and information, instructions, or both that use of the kit will provide treatment for medical conditions in mammals (particularly humans) The kit may include an additional pharmaceutical composition for use in combination therapy. The kit may include buffers, reagents, or other components to facilitate the mode of administration. The information and instructions may be in the form of words, pictures, or both, and the like. In addition, or in the alternative, the kit may include the compound, a composition, or both; and information, instructions, or both, regarding methods of application of compound, or of composition, preferablywith the benefit of treating or preventing medical conditions in mammals (e.g., humans)In certain aspects, the kit comprises at least one of compounds AMD-1, AMD-2, AMD-3, AMD-4, AMD-5, AMD-6, AMD-7, AMD-8, AMD-9, AMD-10, AMD-11, AMD-12, AMD-13, AMD-14, AMD-15, or pharmaceutically acceptable salts thereof; or a composition comprising at least one of compounds AMD-1, AMD-2, AMD-3, AMD-4, AMD-5, AMD-6, AMD-7, AMD-8, AMD-9, AMD-10, AMD-11 , AMD-12, AMD-13, AMD-14, AMD-15, or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier, optionally further comprising information or instructions for use, optionally further comprising buffers, reagents, or other components to facilitate the mode of administration.In certain aspects, the kit comprises the compound AMD-10 (Formula XI), or a pharmaceutically acceptable salt thereof, or a composition comprising AMD-10 (Formula XI) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier and instructions for use.ExamplesThe inventors have designed and synthesized a series of amphiphilic sulfonyl-y- AApeptide foldamers (FIG. 1D), incorporating both cationic and hydrophobic residues, to systematically evaluate their antibacterial activity against multidrugresistant bacterial strains. Notably, compound AM 10, which remains stable across a range of physiological conditions, demonstrated potent antimicrobial efficacy, effectively eliminating six bacterial pathogens and significantly inhibiting biofilm formation without inducing the development of resistance. Mechanistic investigations revealed that antibacterial effect of AM 10 is primarily mediated via membrane disruption, accompanied by the induction of reactive oxygen species (ROS) accumulation. Additionally, in vivo assessments substantiated the therapeutic potential of sulfonyl-y-AApeptide foldamers, confirming their capability to eradicate drug-resistant bacterial infections and providing a promising framework for the future development of antimicrobial therapies aimed at combating resistant bacterial strains.The following non-limiting examples illustrate exemplary systems and components thereof in accordance with various embodiments of the disclosure. The examples are merely illustrative and are not intended to limit the disclosure in any way.Example 1 - Design and Antimicrobial Activity of Right-handed Sulfonyl-y-AApeptide FoldamersNatural a-helical AMPs typically exist in disordered, random coil conformation in aqueous solution but undergo a transition to an a-helical structure upon interaction with lipid membranes This conformational adaption promotes spatial segregation of hydrophobic and hydrophilic residues, thereby generating amphipathic helices that facilitate membrane insertion and disruption. Interestingly, sulfonyl-y-AApeptides adopt well-defined secondary structures with intrinsic helical folding propensities, which arise from intramolecular hydrogen bonding between sulfonamido moieties along the backbone (FIG. 2). As revealed in the crystal structures, the homogeneous D-sulfonyl-y-AApeptides adopt a right-handed helical conformation with a pitch of 51 A and 4 side chains per turn, closely resembling the structural parameters of natural a-helix (5.4 A pitch and 3.6 residues per turn). Considering these facts, systematic modification of both chiral and achiral side chains with hydrophobic or hydrophilic substituents could generate amphipathic helical architectures capable of exhibiting broad-spectrum antimicrobial activity through disruption of bacterial membrane integrity.A series of homogeneous 8-mer D-sulfonyl-y-AApeptides sequences were rationally designed by incorporating hydrophobic substituents and cationic amine functionalities along the backbone (FIG. 3). All building blocks and sequences were synthesized according to previously reported methods and purified and characterized by RP-HPLC.Their antimicrobial activities were evaluated against six bacterial strains by determining minimum inhibitory concentration (MIC), enabling systematic analysis of structure-activity relationships and sequence optimization (Table 1). All sequences were designed with free N terminus, consistent with the characteristics of many natural a-helical AMPs.Table 1. Antimicrobial activity of sulfonyl-y-AApeptidesCmpd Gram-positive Gram-negative MRSA MRSE E~F. E. coll K . P AM1 >25 125 >25 125 ^25 ^25~ AM2 12.5 6.25 25 6.25 >25 6.25AM3 12.5 6.25 >25 12.5 >25 >25 AM4 >25 12.5 >25 6.25 >25 >25 AM5 >25 12.5 >25 12.5 >25 >25 AM6 625 12.5 12.5 12.5 >25 12.5 AM7 >25 25 >25 25 >25 >25 AM8 625 625 625 625 >25 625 AM9 12.5 6.25 12.5 25 >25 12.5 AM10 3.12 3.12 1.56 3.12 6.25 6.25 AM11 3 12 3.12 3.12 25 12.5 6.25 AM12 625 3.12 1.56 25 25 12.5 AM13 625 6.25 6.25 25 >25 >25 AM14 12.5 12.5 12.5 >25 >25 25 AM 15 >25 25 12.5 >25 >25 >25 Cipro 024 0.45 0.9 0.12 0.9 0.45In compounds AM1-AM3, hydrophobic phenyl groups were spatially aligned on one chiral helical surface (positions 1a, 3a, 5a, and 7a), while cationic amine groups were distributed on the opposing chiral surface (positions 2a, 4a, 6a, and 8a), thereby generating amphipathic helical architectures. A modest enhancement in antimicrobial activity was observed upon increasing hydrophobicity through replacement of methyl sulfonyl groups with benzyl sulfonyl substituents, whereas introduction of the positively charged sulfonyl aminoethyl markedly diminished activity. Furthermore, compounds AM5, AM7 and AM8 were designed to align hydrophobic and cationic residues on two achiral surfaces Among these, AM8, featuring a repeating hydrophobic-positive motif on the chiral surface exhibited enhanced activity against gram-positive pathogens. In contrast, AM4 and AM6, which lacked well-defined amphipathic surface segregation, displayed negligible antimicrobial activity.Guided by these observations, AM10 and AM11 were subsequently designed to maintain similar hydrophobic and cationic compositions while orienting these residues on opposing helical surfaces. Both compounds demonstrated potent and broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria. Using AM10 as a lead scaffold, additional analogues (AM12-AM15) weregenerated by modulating hydrophobicity through incorporation of less hydrophobic residues (e.g , tryptophan) or more hydrophobic substituents, including chlorobenzene sulfonyl and naphthalene sulfonyl groups. However, these modifications did not result in further improvement in antimicrobial potency.Amphipathicity is a critical determinant of membrane selectivity and disruption in natural AMPs, however excessive amphipathicity is often associated with hemolytic toxicity, which is a major hurdle for clinical use of AMPs. Thus, the hemolytic activities of representative compounds AM10-AM13 were evaluated. The half maximal hemolytic concentration (HCso) and selective index (SI) were determined (Table 2). Notably, AM10 exhibited the most favorable SI, indicating a strong preference for bacterial membranes over mammalian red blood cells.Table 2. Hemolytic activity and selective index of antimicrobial sulfonyl-y-AA peptidesCompd. MIC (pg / mL) HCso (pg / mL) Selective Index (SI)MRSA E. coli MRSA E. coli AM10 3.12 3.12 2257 72.34 72.34 AM11 3.12 25 162.2 51.99 6.49 AM12 6.25 25 247 39.52 9.88 AM13 6.25 25 1799 28.78 7.20Additionally, the minimum bactericidal activity (MBC) of AM10 was assessed, revealing complete eradication of most bacterial growth at 2x MIC for five strains and effective elimination of MRSE at 1x MIC (Table 3). Collectively, these results identify AM10 as a promising lead candidate for further mechanistic and preclinical investigation.Table 3. Minimal bactericidal activity of the lead compound AM10 against six pathogensMBC (pg / mL)Gram-positive Gram-negativeExample 2 - Time-kill kinetics, Drug resistance and Anti-biofilm StudyThe bactericidal efficacy of AM 10 against E. coli and MRSA was assessed by using time-kill kinetics assays (FIG. 4A, B). Treatment at 1x MIC resulted in growth inhibition without complete eradication, whereas exposure to 2x MIC initiated rapid bactericidal activity, leading to substantial elimination of E. coli within 60 min.Increasing the concentration to 4x MIC further accelerated bacterial killing, achieving complete eradication within 10 min. A comparable concentration and time-dependent killing profile was observed against MRSA, with complete bacterial elimination occurring within 30 min at 4x MIC. These results demonstrated the rapid and potent bactericidal activity of helical foldamer AM10 against both Gram-negative and Grampositive pathogens.Given the widespread emergence of antibiotic resistance driven by diverse adaptive mechanisms, the propensity of compound AM 10 to induce resistance was further evaluated through serial passage experiments (FIG. 4C, D). The MIC of AM10 against E. coli remained unchanged over 14 consecutive passages, in stark contrast to ciprofloxacin, which induced an approximately 300-fold increase over the same period. Similarly, MRSA failed to develop detectable resistance to AM10 after 16 passages, whereas treatment with ciprofloxacin resulted in a 30-fold elevation in MICThese findings indicated a lower propensity for resistance development, consistent with membrane-disruptive mechanism of action characteristic of amphipathic helical AMPs.In addition to planktonic bacterial killing, the antibiofilm activity of AM10 was investigated, as biofilm formation significantly contributes to bacterial persistence, therapeutic failure and increased clinical mortality. Treatment with AM 10 effectively inhibited biofilm formation in both E. coli and MRSA, achieving more than 80% of reduction in biofilm biomass at a concentration of 7.5 pg / mL. (FIG. 5) Collectively, these results highlighted the rapid bactericidal kinetics, resistance-refractory profile, and potent antibiofilm activity of AM10, underscoring its promise as a robust antimicrobial agent for combating drug-resistant bacterial infections.Example 3 - Mechanism of ActionT o elucidate the mechanism of action of designed helical foldamers and to verify their proposed membrane-disruptive behavior analogous to that of natural AMPs, a series of membrane-focused mechanistic studies were conducted. Because Gram-negative bacteria possess both an outer and an inner membrane, whereas Gram-positive bacteria contain a single cytoplasmic membrane, complementary assays were employed to probe membrane integrity in representative strainsOuter membrane permeabilization in E. coli was first evaluated using N-phenylnaphthylamine (NPN) uptake assay. NPN is a hydrophobic fluorescent probe that is excluded by an intact membrane but exhibits enhanced fluorescence upon membrane disruption and subsequent partitioning into the lipid bilayer. Treatment with AM 10 (Fig.6A) resulted in a pronounced and concentration-dependent increase in NPN fluorescence over a 2 h period at concentrations ranging from 1x to 8x MIC, indicating effective compromise of the outer membrane. Melittin, a well-characterized lytic AMP, was included as a positive control and produced the expected fluorescence enhancement.Disruption of the inner membrane of E. coli was subsequently assessed using the Ortho-nitrophenyl p-d-galactopyranoside (ONPG) assay (Fig. 6B). Under normal conditions, ONPG is unable to cross the cytoplasmic membrane. However, membrane permeabilization permits its intracellular entry and enzymatic cleavage by p-galactosidase to generate ortho-nitrophenol, which can be quantified spectrophotometrically at 420 nm. Upon exposure to AMD-10 concentrations from 1x to 8x MIC, a time- and dose-dependent increase in absorbance was observed over 3 h, conforming significant perturbation of inner membrane integrity.Since maintenance of membrane potential is essential for bacterial viability, membrane depolarization was further examined using the voltage-sensitive dye 3,3'-dipropylthiadicarbocyanine iodide DiSCs(5) (Fig. 6C, D). In polarized membranes, DiSCs(5) accumulates intracellularly and undergoes self-quenching, whereas membrane depolarization results in dye release and a concomitant increase in fluorescence. E. coli cells preloaded with DiSC3(5) exhibited a rapid and marked fluorescence increase following treatment with AM 10, indicative of membrane depolarization. Notably, at 4x MIC, AM10 induced a stronger depolarization response than melittin. Consistent results were obtained in MRSA, demonstrating effective disruption of cytoplasmic membrane in Gram-positive bacteria with pronounced fluorescence changes observed at 8x MIC.To directly visualize membrane damage, transmission electron microscopy (TEM) was employed (Fig. 7A). Both E. coli and MRSA cells treated with AM10 exhibited severe morphological abnormalities, including disrupted membrane and compromised cell envelopes, in contrast to the intact membrane structures observed in untreated controls. These ultrastructural changes provided direct evidence of membrane-targeted bactericidal activity.Moreover, fluorescence confocal microscopy was used to assess bacterial viability following treatment (Fig. 7B). Bacterial cells were stained with 4’6’-diamidino-2-phenylindole (DAPI) to label nucleic acids and propidium iodine (PI), which selectively penetrates membrane-compromised, nonviable cells. After 3 h of exposure to AM 10, both E. coli and MRSA populations displayed extensive PI uptake, indicating complete loss of membrane integrity and cell death, while untreated bacteria remained Pl-negative, and the following DAPI / PI staining, it’s observed all bacterial cells were killed under confocal microscopy while the bacterial cells without treatment stayed live without any PI signal. Overall, these mechanistic studies demonstrated that AM 10 exerted its antimicrobial activity primarily through rapid and extensive disruption of bacterial membrane integrity, leading to membrane depolarization, leakage of intracellular components and ultimately cell death.Reactive oxygen species (ROS), including superoxide anions and hydrogen peroxide, are inevitable byproducts of aerobic bacterial respiration and are normally rightly regulated by endogenous antioxidant systems However, membrane perturbation caused by antimicrobial peptides could induce metabolic dysregulation, making ROS induced by AMPs can disrupt cellular homeostasis and metabolic processes, leading to excessive ROS accumulation that contributes to bacterial lethality as a secondary and synergistic mechanism In the present study, intracellular ROS generation was assessed using cell-permeable, non-fluorescent probe 2', 7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), which is oxidized to the highly fluorescent dichlorofluorescein (DCF) upon reaction with ROS and quantified using a plate reader Treatment with compound AM 10 resulted in obvious and dosedependent increase in DCF fluorescence signal in both E. coli and MRSA (Fig. 8A, B) Meanwhile, co-incubation with ROS scavenger N-acetylcysteine (NAC) at the highest compound concentration markedly attenuated the fluorescence signal to levels comparable to untreated control group, thereby confirming ROS accumulation as an important complimentary mechanism to bacterial membrane disruption in AM 10 mediated bacterial killing.Given that respiratory electron transport chain (ETC), the primary intracellular source of ROS, is located to the cytoplasmic membrane, it’s reasonable to hypothesize that membrane distraction may directly impair the ETC function, thereby promoting ROS overproduction Dehydrogenases serve as the initial and essential enzymes of ETC; thus, their activity was examined to elucidate the impact of AM 10 treatment on bacterial respiration in E. coli and MRSA (Fig.8C, D). Consistent with this hypothesis, AM 10 treatment led to a significant and dose-dependent inhibition of respiratory dehydrogenase activity in both strains. Moreover, a more pronounced inhibitory effect was observed in MRSA compared with E. coli, correlating well with the higher DCF fluorescence intensity detected in MRSA cells. These findings collectively support a mechanistic link between membrane rupture, respiratory chain dysfunction, and ROS accumulation, ultimately contributing to bacterial cell death.Example 4 - Cell Viability and In vivo EfficacyPrior to evaluating the in vivo antibacterial efficacy, it’s crucial to assess the cytotoxicity of the candidate compound toward to mammalian cells. Accordingly, the cytocompatibility of AM 10 was examined using HeLa cells treated with different concentrations, and cell viability was quantified via CCK-8 assay (Fig. 9A). Notably, more than 85% of cells remained viable at a concentration of 62.5 pg / mL, indicating minimal cytotoxicity and highlighting the favorable safety profile and pharmaceutical potential of AM 10.Example 5- In vivo studyIn vivo study is a critical step in validating the therapeutical applicability of AMPs, as it provides insight into their efficacy against clinically relevant infections, as well as their systemic toxicity and pharmacokinetic behavior. The mouse thigh infection model was employed to investigate in vivo antibacterial activity of AM10. (FIG. 9B) The in vivo experiments were carried out following the protocol approved by Institutional Animal Care and Use Committee (IACUC) of University of South Florida. CD-1 mice (6-8 weeks old, 2 male, 2 female per group) were neutropenic by intraperitoneal (i.p.) administration of cyclophosphamide (300 mg / kg) on Day 1 and Day 4 prior to bacterial inoculation. Each mouse was inoculated via intramuscular injecting of 100 pL of MRSA suspension (10® CFU / mL) into each thigh. Mice were treated with AM10 or ciprofloxacin (10 mg / kg) at 1 h and 13 h post-infection. Ciprofloxacin (10 mg / kg), an FDA-approved small molecule antibiotic, was included as positive control. All mice were euthanized 25 h after inoculation, and both thighs were harvested and homogenized for approximately 30 s. Tissue homogenates wereserially diluted and plated (100 pL) onto tryptic soy agar. Plates were incubated at 37 °C for 20 h, and bacterial burden was quantified by calculating colony-forming units (CFU / mL).Treatment with AM10 resulted in a 1.5-Logio reduction in bacterial burden, compared with a 2-Log-io reduction observed for ciprofloxacin. (FIG. 9C) These results demonstrated that AM10 exhibited substantial in vivo antibacterial efficacy, supporting the therapeutic promise of the foldamer-based antimicrobials for the treatment of resistant bacterial infections.Example 6 - Treatment of MRSA Bacterial Infection (prophetic)A 35 year old female patient presents with red, swollen, pus-filled sores on the skin as well as fever and chills. A culture is taken and MRSA is diagnosed. The patient is parenterally administered a therapeutically effective amount of AMD-10. The patient’s symptoms are reduced after a therapeutically effective amount of time.Example 7 - Treatment of MRSE Bacterial Infection (prophetic)A 40 year old male patient presents with blisters on the skin as well as nausea. A culture is taken and MRSE is diagnosed. The patient is parenterally administered a therapeutically effective amount of AMD-10. The patient’s symptoms are reduced after a therapeutically effective amount of time.Example 8- T reatment of VREF Bacterial Infection (prophetic)A 38 year old male patient presents with frequent urination and burning sensation. A urine sample is collected and analyzed, and VREF is diagnosed. The patient is orally administered a therapeutically effective amount of AMD-10. The patient’s symptoms are reduced after a therapeutically effective amount of time.Example 9 - Treatment of E. coli Bacterial Infection (prophetic)A 43 year old female patient presents with abdominal cramps, nausea, and watery diarrhea A fecal sample is collected and analyzed, and an E coli infection is diagnosed. The patient is orally administered a therapeutically effective amount of AMD-10. The patient’s symptoms are reduced after a therapeutically effective amount of time.Example 10 - Treatment of Enterococcus faecalis Bacterial Infection (prophetic)A 40 year old male patient presents with pain during urination, frequent urination and cloudy urine. A urine sample is collected and analyzed, and an Enterococcus faecalis infection is diagnosed. The patient is orally administered a therapeutically effective amount of AMD-10. The patient’s symptoms are reduced after a therapeutically effective amount of time.Example 11 - Treatment of Pseudomonas aeruginosa Bacterial Infection (prophetic)A 28 year old female patient presents with earache and fluid discharge from the ear. A sample is collected and analyzed, and a Pseudomonas aeruginosa infection is diagnosed. The patient is otically administered a therapeutically effective amount of AMD-10. The patient’s symptoms are reduced after a therapeutically effective amount of time.Example 12 - Treatment of Klebsiella pneumoniae Bacterial Infection (prophetic)A 60 year old male patient presents with cough, shortness of breath, and fever. A sample is collected and analyzed, and a Klebsiella pneumoniae infection is diagnosed. The patient is orally administered a therapeutically effective amount of AMD-10. The patient’s symptoms are reduced after a therapeutically effective amount of time.ConclusionThe escalating prevalence of antibiotic resistance represents a critical and persistent threat to global public health, necessitating the development of alternative antimicrobial strategies. Although natural AMPs exhibit broad-spectrum activity predominantly through membrane-disruptive mechanisms that limit resistance development, their clinical transition has been hindered by poor stability and undesirable cytotoxicity. Addressing these limitations while preserving antimicrobial efficacy remains an urgent unmet need The inventors have developed a class of homogeneous D-sulfonyl-y-AApeptides that adopt a well-defined right-handed helical conformation, effectively mimicking the structural and functional attributes of natural a-helical AMPs. Through systematic modulation of chiral and achiral side chains incorporating hydrophobic and cationic functionalities, optimal amphiphilicity wasachieved, leading to the identification of lead compound AM10. AM 10 exhibited potent and broad-spectrum antibacterial activity, coupled with favorable selectivity toward bacterial over mammalian cells in lysis effects, and a promising therapeutic index. Beyond bactericidal activity, AM10 effectively inhibited biofilm formation and exhibited a low propensity for resistance development during prolonged exposure. Notably, these unnatural foldamers displayed exceptional stability under physiological salts conditions and retained integrity in the presence of enzyme and serum. Mechanistic investigations revealed that AM 10 exerted its antibacterial effect primarily via membrane disruption, as evidenced by increased membrane permeability, membrane depolarization and morphological damage to bacterial cells. Moreover, AM 10 induced excessive ROS accumulation by perturbing dehydrogenase activity within bacterial respiratory chain. Importantly, the low cytotoxicity of AM 10 enabled effective suppression of MRSA infections in mice model, underscoring its therapeutic potential in vivo.In conclusion, these findings establish the right-handed sulfonyl-y-AApeptides as a promising class of antibacterial agents, expanding the biological applications of helical peptidomimetics beyond protein-protein interaction modulation. This work further broadens the chemical diversity and application scope of unnatural foldamer scaffolds in antimicrobial developmentReferences(1) Wertheim, H.; Pulcini, C.; Johnstone, F.; Schouten, J.; Kanj, S S.; Skov, R. Establishing the pivotal role of infectious diseases and clinical microbiology professional societies: A global survey. J Glob Antimicrob Re 2025, 45.(2) Salam, M. A.; Al-Amin, M. Y.; Salam, M. T.; Pawar, J. S.; Akhter, N.; Rabaan, A. A.; Alqumber, M. A. A Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare 2023, 11 (13), 1946.(3) Iskandar, K.; Murugaiyan, J ; Hammoudi Halat, D.; Hage, S. E.; Chibabhai, V.; Adukkadukkam, S.; Roques, C.; Molinier, L.; Salameh, P.; Van Dongen, M. Antibiotic Discovery and Resistance: The Chase and the Race. Antibiotics 2022, 11 (2), 182. (4) Langford, B J.; Soucy, J. P. R.; Leung, V ; So, M.; Kwan, A. T. H.; Portnoff, J S.; Bertagnolio, S.; Raybardhan, S ; MacFadden, D. R.; Daneman, N. Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and metaanalysis. Clin Microbiol Infec 2023, 29 (3), 302-309.(5) Naghavi, M.; Vollset, S. E.; Ikuta, K. S.; Swetschinski, L. R.; Gray, A. P.; Wool, E. E.; Robles Aguilar, G.; Mestrovic, T.; Smith, G.; Han, C.; et al. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. The Lancet 2024, 404 (10459), 1199-1226.(6) Kang, M. W.; Ahn, S. Y. Optimising personalised antibiotic treatment for methicillin-resistant bloodstream infections in ICU patients using a deep learningbased causal inference approach. J Glob Antimicrob Re 2025, 45, 70-76.(7) Asantewaa, A. A.; Yartey, S. N. A.; Donkor, E. S. A systematic review and metaanalysis of the risk of mortality associated with methicillin-resistant clones. J Glob Antimicrob Re 2025, 45, 86-99.(8) Yassin, A.; Eid, R. A.; Mohammad, M F.; Elgendy, M. O.; Mohammed, Z.; Abdelrahim, M. E. A.; Abdel Hamied, A. M.; Binsuwaidan, R.; Saleh, A ; Hussein, M.; et al. Microbial Multidrug-Resistant Organism (MDRO) Mapping of Intensive Care Unit Infections. Medicina 2025, 61 (7), 1220.(9) Sun, S. Emerging antibiotic resistance by various novel proteins / enzymes. European Journal of Clinical Microbiology & Infectious Diseases 2025, 44 (7), 1551-1566(10) Darby, E. M.; Trampari, E.; Siasat, P.; Gaya, M. S.; Alav, I.; Webber, M. A.; Blair, J. M. A. Molecular mechanisms of antibiotic resistance revisited. Nature Reviews Microbiology 2023, 21 (5), 280-295.(11) Le, C.-F.; Fang, C.-M.; Sekaran, S. D. Intracellular Targeting Mechanisms by Antimicrobial Peptides. Antimicrobial Agents and Chemotherapy 2017, 61 (4), AAC.02340-02316.(12) Brown, E. D.; Wright, G. D. Antibacterial drug discovery in the resistance era. Nature 2016, 529 (7586), 336-343.(13) Zhang, C.; Yang, M. Antimicrobial Peptides: From Design to Clinical Application. Antibiotics 2022, 11 (3), 349.(14) Bechinger, B.; Zasloff, M.; Opella, S J. Structure and orientation of the antibiotic peptide magainin in membranes by solid-state nuclear magnetic resonance spectroscopy. Protein Science 1993, 2 (12), 2077-2084.(15) Zhang, H.-Q.; Sun, C.; Xu, N.; Liu, W. The current landscape ofthe antimicrobial peptide melittin and its therapeutic potential. Frontiers in Immunology 2024, 15. (16) Huang, Y.; Huang, J ; Chen, Y Alpha-helical cationic antimicrobial peptides: relationships of structure and function. Protein & Cell 2010, 1 (2), 143-152. (17) Gan, B. H.; Gaynord, J.; Rowe, S. M.; Deingruber, T.; Spring, D. R. The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions. Chemical Society Reviews 2021, 50 (13), 7820-7880.(18) Wang, G.; Narayana, J. L.; Mishra, B.; Zhang, Y.; Wang, F.; Wang, C.; Zarena, D.; Lushnikova, T.; Wang, X. Design of Antimicrobial Peptides: Progress Made with Human Cathelicidin LL-37. Springer Singapore, 2019; pp 215-240.(19) Su, M.; Su, Y. Recent Advances in Amphipathic Peptidomimetics as Antimicrobial Agents to Combat Drug Resistance. Molecules 2024, 29 (11 ), 2492. (20) Xie, J.; Hu, W.; Feng, X.; Liu, Z.; Zhou, M.; Liu, R Synthesis and antimicrobial applications of a-peptoid polymers. Chemical Science 2025, 16 (28), 12679-12701. (21) Bahatheg, G.; Kuppusamy, R.; Hartmann, L; Cranfield, C. G.; Black, D. S.; Willcox, M D. P.; Kumar, N. Antibacterial peptidomimetics based on guanidine-functionalized di-tertiary amides RSC Medicinal Chemistry 2025.The disclosures of all publications cited above are expressly incorporated herein by reference, each in its entirety, to the same extent as if each were incorporated by reference individually.While certain aspects of conventional technologies have been discussed to facilitate disclosure of the invention, Applicants in no way disclaim these technical aspects, and it is contemplated that the claimed invention may encompass one or more ofthe conventional technical aspects discussed hereinThe present invention may address one or more ofthe problems and deficiencies of the prior art discussed above However, it is contemplated that the invention may prove useful in addressing other problems and deficiencies in a number of technical areas. Therefore, the claimed invention should not necessarily be construed as limited to addressing any ofthe particular problems or deficiencies discussed herein.In this specification, where a document, act or item of knowledge is referred to or discussed, this reference or discussion is not an admission that the document, act or item of knowledge or any combination thereof was at the priority date, publicly available, known to the public, part of common general knowledge, or otherwise constitutes prior art under the applicable statutory provisions; or is known to be relevant to an attempt to solve any problem with which this specification is concerned. It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described, and all statements of the scope of the invention which, as a matter of language, might be said to fall there between. Now that the invention has been described,

Claims

What is claimed is:

1. A compound comprising Formula (I), or a pharmaceutically acceptable salt thereof:(Diwherein R1 is independently selected fromwherein R2 is independently selected from; andwherein n is an integer from 1 to 8.

2. The compound of claim 1 , wherein n is 8.

3. A compound comprising Formula (II), or a pharmaceutically acceptable salt thereof:(II).4 A compound comprising Formula (III), or a pharmaceutically acceptable saltthereof:(HI).

5. A compound comprising Formula (IV), or a pharmaceutically acceptable saltthereof:

6. A compound comprising Formula (V), or a pharmaceutically acceptable saltthereof:

7. A compound comprising Formula (VI), or a pharmaceutically acceptable salt thereof:(VI).

8. A compound comprising Formula (VII), or a pharmaceutically acceptable saltthereof:(VII).

9. A compound comprising Formula (VII), or a pharmaceutically acceptable saltthereof:(VIII).

10. A compound comprising Formula (IX), or a pharmaceutically acceptable saltthereof:(IX).11 A compound comprising Formula (X), or a pharmaceutically acceptable salt thereof:

12. A compound comprising Formula (XI), or a pharmaceutically acceptable salt thereof:(XI).

13. A compound comprising Formula (XII), or a pharmaceutically acceptable salt thereof:

14. A compound comprising Formula (XIII), or a pharmaceutically acceptable salt thereof:(XIII).

15. A compound comprising Formula (XIV), or a pharmaceutically acceptable saltthereof:

16. A compound comprising Formula (XV), or a pharmaceutically acceptable saltthereof:

17. A compound comprising Formula (XVI), or a pharmaceutically acceptable saltthereof:(XVI).

18. A pharmaceutical composition comprising the compound of any of claims 1-17 and a pharmaceutically acceptable carrier19. A method of treating a bacterial infection in a patient in need thereof comprising:administering to the patient a therapeutically effective amount of the compound of any of claims 1-17 or the pharmaceutical composition of claim 18;wherein the therapeutically effective amount of the pharmaceutical composition exerts bactericidal and / or bacteriostatic effects on the bacterial infection to treat the bacterial infection.20 A method of inhibiting biofilm formation in a bacterial infection in a patient in need thereof, the method comprising:administering to the patient a therapeutically effective amount of the compound of any of claims 1-17 or the pharmaceutical composition of claim 18;wherein the therapeutically effective amount of the compound or the pharmaceutical composition inhibits biofilm formation.

21. The method of claim 19 or 20, wherein the compound is the compound of claim 12.

22. The method of claim 19 or 20, wherein the pharmaceutical composition comprises the compound of claim 12, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

23. The method of any of claims 19-22, wherein the bacteria is Gram positive (Gram (+)) bacteria.24 The method of any of claims 19-23, wherein the Gram (+) bacteria comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, and / or Streptococcus pneumoniae.

25. The method of any of claims 19-22, wherein the bacteria is Gram negative (Gram -) bacteria.

26. The method of claim 25, wherein the Gram negative bacteria comprises Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillus moniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, and / or Yersinia enterocolitica.

27. The method of any of claims 19-22, wherein the bacteria is a drug-resistant bacteria.

28. The method of claim 27, wherein the drug-resistant bacteria comprises methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem- resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.

29. A method of inducing bacteria death comprising:contacting the bacteria with an effective amount of the compound of any of claims 1-1730. A method of increasing membrane permeability in a bacterium comprising:contacting the bacterium with an effective amount of the compound of any of claims 1-17.

31. A method of inducing membrane depolarization in a bacterium comprising:contacting the bacterium with an effective amount of the compound of any of claims 1-17.

32. A method of inducing membrane disruption in a bacterium comprising:contacting the bacterium with an effective amount of the compound of any of claims 1-17.

33. A method of inducing reactive oxygen species (ROS) accumulation in a bacterium comprising:contacting the bacterium with an effective amount of the compound of any of claims 1-17.

34. The method of any of claims 29-33, wherein the bacterium comprises Actinomedurae, Actinomyces israelii, Bacillus anthracis, Bacillus cereus, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Nocardia, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epiderm, Streptococcus mutans, Streptococcus pneumoniae, Afipia felis, Bacteriodes, Bartonella bacilliformis, Bortadella pertussis, Borrelia burgdorferi, Borrelia recurrentis, Brucella, Calymmatobacterium granulomatis, Campylobacter, Escherichia coli, Francisella tularensis, Gardnerella vaginalis, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenziae, Heliobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Neisseria meningitidia, Porphyromonas gingivalis, Providencia sturti, Pseudomonas aeruginosa, Salmonella enteridis, Salmonella typhi, Serratia marcescens, Shigella boydii, Streptobacillusmoniliformis, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, Yersinia enterocolitica, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), or vancomycin-resistant Enterococcus faecium (VREF), fluoroquinolone-resistant Salmonella typhi or Salmonella enteridis, cephalosporin / fluoroquinolone-resistant Neisseria gonorrhoeae, clarithromycin-resistant Helicobacter pylori, ampicillin-resistant Haemophilius influenzae, penicillin-non-susceptible Streptococcus pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumonae, carbapenem-resistant Escherichia coli, carbapenem- resistant Pseudomonas aeruginosa, and / or rifampicin-resistant Mycobacterium tuberculosis.

35. A kit comprising:the compound of any of claims 1-17 or the pharmaceutical composition of claim 18; andinstructions for use

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