32 results about "Carbapenem resistant" patented technology

The invention discloses an antibacterial peptide based on D-type amino acid and application of the antibacterial peptide, and the antibacterial peptide is characterized in that the amino acid sequence is w-r-r-w-r-r-w-w-r-k-r (dTrp-dArg-dArg-dTrp-dArg-dArg-dTrp-dTrp-dArg-dLys-dArg). The antibacterial peptide can be synthesized through an Fmoc solid-phase chemical method, the synthesis difficulty is low, and the in-vivo antibacterial activity is good. The antibacterial peptide especially has broad-spectrum killing activity on carbapenem-resistant pseudomonas aeruginosa, pseudomonas aeruginosa, klebsiella pneumoniae, escherichia coli, methicillin-resistant staphylococcus aureus and staphylococcus aureus, is low in hemolytic toxicity, can reach half or more of cell survival rate under medium and low concentration, almost has no toxic effect on cells, and can be used for preparing the antibacterial peptide with a broad-spectrum killing activity on carbapenem-resistant pseudomonas aeruginosa, klebsiella pneumoniae, escherichia coli, methicillin-resistant staphylococcus aureus and staphylococcus aureus. The stability is good, the operability is high, and the cost is low.

The invention discloses a deoxyribozyme probe for identifying carbapenem-resistant klebsiella pneumoniae and application of the deoxyribozyme probe, and belongs to the technical field of deoxyribozyme probes. The method comprises the following steps: firstly, mixing a phosphorylated library chain, a substrate chain and a connecting chain, then, carrying out covalent linkage to construct a DNA library, firstly, carrying out reverse screening, separating and purifying a DNA band of an uncut substrate RNA site, constructing a chain-shaped DNA library by using the obtained DNA band, carrying out forward screening, separating and purifying the DNA band of the cut substrate RNA site, carrying out PCR (Polymerase Chain Reaction) amplification, and recovering a positive-sense chain, so as to obtain the DNA library. The deoxyribozyme probe is obtained by performing repeated screening and enriching, and the probe can recognize carbapenem-resistant klebsiella pneumoniae with high specificity and has the potential of exerting advantages in the aspect of biosensing application.

The invention discloses an application of an antibacterial peptide and an application of the antibacterial peptide in preparation of antibacterial drugs for treating carbapenem-resistant pseudomonas aeruginosa, klebsiella pneumoniae (ATCC700603), escherichia coli (ATCC25922), staphylococcus aureus and methicillin-resistant staphylococcus aureus, the antibacterial peptide is characterized in that the sequence is w-r-r-w-k-r-w-w-r-r, and the sequence is shown in the description. All amino acids are D-type amino acids; the antibacterial peptide can be used as an antibacterial substance in wash supplies, food preservative additives, medical consumable antibacterial agents and cosmetics, can be synthesized through an Fmoc solid-phase chemical method, and is low in synthesis difficulty and good in in-vivo antibacterial activity. Particularly, the antibacterial peptide has broad-spectrum killing activity against carbapenem pseudomonas aeruginosa, klebsiella pneumoniae (ATCC700603), escherichia coli (ATCC25922), staphylococcus aureus and methicillin-resistant staphylococcus aureus, the cell survival rate of the antibacterial peptide within the range of medium and low concentration (2 mu g / mL-32 mu g / mL) reaches half or more, the toxicity is small, the toxicity is almost avoided, the operability is high, and the antibacterial peptide can be widely applied to the field of medical application. The cost is low.

The invention relates to an antibacterial peptide LK-KJT-B01 for gram-negative bacterium infection and a preparation method and application thereof.The antibacterial peptide LK-KJT-B01 can be extracted from bacillus laterosporus, has the advantages of being broad in spectrum, safe, free of toxicity and the like, has a very strong bactericidal effect on gram-negative bacterium infection, and can be used for preparing antibacterial peptide LK-KJT-B01 for gram-negative bacterium infection. Particularly, the sensitivity to carbapenem-resistant gram-negative bacteria is high, and the application prospect is very wide.

The invention discloses application of lactobacillus plantarum LP-Y01 and a fungicide thereof in preparation of a medicine for preventing and / or treating carbapenem-resistant drug-resistant bacterium infection. The invention verifies that the lactobacillus plantarum can generate a direct inhibition effect on carbapenem-resistant klebsiella pneumonia in vitro and has certain effective activity on colonization of the carbapenem-resistant klebsiella pneumonia in vivo through flora regulation and control. Probiotic pretreatment shows remarkable clinical potential by regulating and controlling a flora structure, provides a precise strategy for prevention and control of drug-resistant bacteria, and has a relatively good application prospect.

The present invention belongs to the field of microbiology and genetics technology, and in particular relates to a primer set and typing detection method and kit for detecting drug-resistant enzyme genes of bacterial strains, wherein the primer set is an amplification primer for β-lactamase-resistant genes and carbapenemase-resistant genes, wherein the β-lactamase-resistant genes include SHV, TEM, and CTX-M, and the carbapenemase-resistant genes include NDM, OXA-23, and KPC. PCR amplification is performed according to specific enzyme typing primers, and genomic DNA is extracted using a magnetic bead method to improve the efficiency and purity of DNA extraction, thereby optimizing the accuracy and efficiency of PCR. The specific enzyme typing results are confirmed by comparison with the NCBI database through agarose gel electrophoresis and subsequent sequencing analysis. The experimental process is simplified, the cost is reduced, and a scientific basis is provided for the screening and clinical use of new β-lactamase and carbapenemase inhibitors, with the advantages of high efficiency, accuracy, and cost-effectiveness.

The application discloses a D-type amino acid-based antibacterial peptide and application thereof, and has the amino acid sequence of w-r-r-w-r-r-w-w-r-k-r (dTrp-dArg-dArg-dTrp-dArg-dArg-dTrp-dTrp-dArg-dLys-dArg). The antibacterial peptide can be synthesized by Fmoc solid-phase chemical synthesis, has low synthesis difficulty, and has good in-vivo antibacterial activity. The antibacterial peptide has broad-spectrum killing activity on carbapenem-resistant pseudomonas aeruginosa, pseudomonas aeruginosa, klebsiella pneumoniae, escherichia coli, methicillin-resistant staphylococcus aureus and staphylococcus aureus, has low hemolytic toxicity, can reach more than half of the cell survival rate at a medium or low concentration, has almost no toxic effect on cells, has good stability, has strong operability, and is low in cost.

The invention relates to the technical field of medicines, in particular to application of combination of meropenem or aztreonam and paromomycin sulfate in preparation of antibacterial drugs. The experimental result of the in vitro combination effect shows that when meropenem or aztreonam is combined with paromomycin sulfate, the meropenem or aztreonam has a remarkable synergistic effect on carbapenem-resistant klebsiella pneumoniae, and paromomycin sulfate can reduce the bacteriostatic concentration of meropenem or aztreonam, so that the meropenem or aztreonam can be used for preparing the medicine for treating the carbapenem-resistant klebsiella pneumoniae. Therefore, the paromomycin sulfate can be used for improving the inhibition effect of meropenem or aztreonam on carbapenem-resistant klebsiella pneumoniae.

This invention belongs to the field of detection technology for carbapenem-resistant Enterobacteriaceae, and provides an anti-KPC-2 carbapenemase nanobody Nb-KPC-2 and its applications. The anti-KPC-2 carbapenemase nanobody Nb-KPC-2 has the amino acid sequence shown in SEQ ID NO.1. This invention lays the foundation for constructing a low-cost and stable immunoassay method for KPC-2 carbapenemases. Utilizing the characteristics of small size, good stability, and ease of labeling, nanobodies can be applied to the rapid detection of pathogenic microorganisms, such as the preparation of diagnostic test strips, reagents, and kits; they can also be applied to basic research and tool development, such as as molecular probes, isolation and purification kits, and the construction of core components for targeted therapy molecules; enabling early and accurate screening and identification of drug-resistant Gram-negative bacteria producing KPC-2 carbapenemases, guiding precise clinical medication and infection control.

The application provides a kind of gold nanocluster and its preparation method and application.The gold nanocluster of the application, the gold nanocluster is tiopronin modified gold nanocluster, the gold nanocluster has gold atom and sulfur atom.The gold nanocluster of the application, the gold nanocluster is tiopronin modified gold nanocluster, the gold nanocluster has gold atom and sulfur atom, can be widely used with antibiotic, has synergistic antibacterial effect, for example, against carbapenem-resistant gram-negative pathogens.The application also provides the preparation method and application of gold nanocluster.

The present invention relates to compositions and methods for detecting Acinetobacter calcoaceticus-Acinetobacter baumannii complex species and identifying the most common carbapenemases found in carbapenem-resistant Acinetobacter calcoaceticus baumannii (CRAB), such as blaOXA-23-like, blaOXA-24-like, blaOXA-58-like, and blaNDM-like, by multiplex real-time PCR assays.

This invention relates to a screening method and application of traditional Chinese medicine inhibitors against carbapenem-resistant Klebsiella pneumoniae, belonging to the field of biomedical technology. Based on a high-throughput screening system for carbapenem-resistant Klebsiella pneumoniae inhibitors constructed using a fluorescent probe for carbapenemase activity detection, the invention successfully screened out mulberry bark as a carbapenemase inhibitor, sanghorn ketone G. When used in combination with meropenem, this inhibitor significantly inhibits the metabolism of meropenem by carbapenem-resistant Klebsiella pneumoniae, greatly enhancing the inhibitory efficiency of meropenem against the strain, providing a highly effective and valuable combination therapy for clinical treatment of carbapenem-resistant Klebsiella pneumoniae infection.

This invention discloses the use of a bacterial membrane dCACHE-type chemokine receptor protein family as a target in the preparation or screening of drugs against multidrug-resistant bacteria, belonging to the field of biomedical technology. This invention reveals and verifies for the first time the core regulatory mechanism of the dCACHE-type chemokine receptor protein family in the bacterial infection process: these proteins are key membrane surface receptors mediating bacterial chemotaxis towards macrophages; their loss of function can directly block bacterial chemotactic movement and significantly reduce pathogenicity. This invention, by targeting the conserved ligand binding interface, successfully inhibited the infectivity of drug-resistant pathogens such as *Yersinia pseudotuberculosis*, carbapenem-resistant *Acinetobacter baumannii*, and carbapenem-resistant *Escherichia coli*. The novel targeting strategy provided by this invention not only effectively overcomes the clinical bottleneck of "no available drugs" for carbapenem-resistant multidrug-resistant bacteria but also constructs a broad-spectrum protective barrier covering the entire homologous protein family, possessing extremely high clinical translational value and commercial development potential.

The invention discloses application of chelerythrine in preparation of drugs or antibiotic synergists for treating bacterial infectious diseases, bacteria are carbapenem antibiotic resistant bacteria, and antibiotics are carbapenem antibiotics. The invention discloses that chelerythrine can restore the sensitivity of carbapenem drug-resistant bacteria for the first time, can reduce the minimum inhibitory concentration of meropenem to bacteria for producing metal beta-lactamase by 16 times, and provides a new strategy for solving the drug resistance of bacteria.

The invention discloses a Ts-ELP temperature-sensitive self-assembly nano fusion protein, an antibiotic delivery system and a preparation method, and belongs to the technical field of nano preparations. The fusion protein comprises antibacterial peptide Ts and elastin-like polypeptide ELP which are sequentially connected. An MMP-9 restriction enzyme cutting site is introduced between the antibacterial peptide Ts and the elastin-like polypeptide ELP. Fusion protein and tigecycline (Tig) are self-assembled to form an antibiotic delivery system, the delivery system has Gram-negative bacterium surface lipopolysaccharide targeted recognition capability, and drug release is triggered through pH response and a phase separation mechanism in an infection microenvironment, so that the enrichment efficiency of tigecycline in a focus area is enhanced, and the drug delivery efficiency is improved. The antibiotic delivery system has the technical advantages of strong targeting property, enhanced antibacterial activity, low drug-resistant induction risk, good biological safety, simple preparation process, high yield and the like, can be used for treatment of multi-drug-resistant bacterium infection, and is especially suitable for prevention and treatment of carbapenem-resistant klebsiella pneumoniae (CRKP) and drug-resistant gram-negative bacterium infection related diseases.

The invention belongs to the technical field of biology, and relates to application of a composition of caerin1.1 / 1.9, caerin1.1 / 1.9 and polymyxin B in treatment of drug-resistant acinetobacter baumannii infection. In the caerin1.1 / 1.9, the mass ratio of the caerin1.1 to the caerin1.9 is 1 to (1 to 3). In the composition, the mass ratio of the caerin1.1 / 1.9 to the polymyxin B is 1: (0.2-3). The amino acid sequences of the caerin1.9 of the caerin1.1 are as shown in SEQ ID No. 1 and SEQ ID No. 2 of the caerin1.1. The composition of the caerin1.1 / 1.9, the caerin1.1 / 1.9 and the polymyxin B plays a role in resisting carbapenem acinetobacter baumannii by reducing the biological membrane of the acinetobacter baumannii, down-regulating the expression of efflux pump genes adeA, adeB and adeC or increasing the pore number of a cell membrane.

The invention belongs to the technical field of bioengineering, and particularly relates to a detection kit for carbapenem-resistant and polymyxin-resistant high-toxicity klebsiella pneumoniae based on ERA-CRISPR / Cas12a and application of the detection kit for the carbapenem-resistant and polymyxin-resistant high-toxicity klebsiella pneumoniae based on the ERA-CRISPR / Cas12a. The invention discloses six target sequences capable of specifically identifying high-toxicity klebsiella pneumoniae resistant to carbapenem and polymyxin, wherein the six target sequences comprise blaNDM-1, mcr-1, iucA, rmpA, iroB and peg-344; a specific detection primer pair of the target sequence is designed. According to the invention, based on the ERA-CRISPR / Cas12a technology, the specific primer pair is utilized to realize rapid and accurate detection of the carbapenem and polymyxin-resistant high-toxicity lebsiella pneumoniae.

The invention discloses a library building method and application of a mass spectrum library for detecting carbapenem-resistant klebsiella pneumoniae producing KPC enzyme, and belongs to the technical field of laboratory medicine. The library building method comprises the following steps: S1, carrying out matrix-assisted laser desorption ionization time-of-flight mass spectrometry detection on carbapenem-resistant klebsiella pneumoniae capable of producing KPC enzyme to obtain mass spectrogram data; s2, preprocessing the mass spectrum data obtained in the step S1, and establishing a basic mass spectrum database to obtain database-established mass spectrum data; s3, performing homology analysis and characteristic peak screening on database-building mass spectrum data obtained in S2, comparing with a strain mass spectrum database, calculating a weight value and a score value, and building a database-building data packet; and S4, activating the database building data packet, storing the database building data packet into a local database, and verifying CRKP-KPC strain mass spectrum identification.

The present invention relates to compositions and methods for the detection of Acinetobacter calcoaceticus-Acinetobacter baumannii complex species and the identification of the most prevalent carbapenem enzymes found in carbapenem resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (CRAB), such as a blaOXA-23 sample, a blaOXA-24 sample, a blaOXA-58 sample, and a blaNDM sample, by multiplex real-time PCR assays.

The invention belongs to the field of biological medicine, and relates to broad-spectrum antibacterial peptide derived from periplaneta americana and anti-tumor application of the broad-spectrum antibacterial peptide. The PA-1 and the PA-2 are both novel alpha-spiral cationic peptides and show remarkable inhibitory activity on pseudomonas aeruginosa, salmonella typhimurium, staphylococcus aureus, staphylococcus epidermidis and carbapenem-resistant acinetobacter baumannii, and the minimum inhibitory concentration on the carbapenem-resistant acinetobacter baumannii reaches 11 [mu] mol / L. In addition, PA-1 and PA-2 can also obviously inhibit the growth of human colon adenocarcinoma cells SW480, cervical cancer cells Hela and gastric cancer cells HGC-27, and show better anti-tumor potential. And the PA-1 and the PA-2 have good thermal stability, pH stability, salt stability and enzyme stability. The two novel active peptides PA-1 and PA-2 provided by the invention show relatively high medicinal values in the antibacterial and anti-tumor fields, and particularly provide a new choice for clinical treatment of carbapenem-resistant acinetobacter baumannii infection.

The present invention relates to antibiotic-resistant bacteria, and to the prevention or treatment of infections of drug-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae (CRE) and / or vancomycin-resistant Enterococcus (VRE). In particular, the invention relates to the treatment or prevention of colonisation of CRE and / or VRE in the gastrointestinal (GI) tract, before they cause invasive infections, for example in the blood. The invention provides novel formulations, pharmaceutical compositions and methods of using them to prevent or treat CRE and / or VRE infections or intestinal colonisations thereof.

Antibiotic resistance leads to deadly hospital-acquired infections globally. The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) have identified priority bacteria, including Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and particularly those carbapenem- resistant strains, also found in Enterobacterales (CRE) such as Escherichia coli and Klebsiella, as requiring new antibiotics. The present disclosure provides a chemical class of drugs less susceptible to existing mechanisms of antibiotic resistance and targeting difficult-to-treat bacterial infections. It more particularly provides compounds of formula (I), and compositions and uses thereof.

The invention belongs to the technical field of carbapenem-resistant enterobacter spp. Bacterium detection, and provides an anti-KPC-2 type carbapenemase nano antibody Nb-KPC-2 and application of the anti-KPC-2 type carbapenemase nano antibody Nb-KPC-2. The anti-KPC-2 type carbapenemase nano antibody Nb-KPC-2 has an amino acid sequence as shown in SEQ ID NO. 1, and the amino acid sequence is as shown in SEQ ID NO. 2. The invention lays a foundation for constructing an immunoassay method of KPC-2 type carbapenemase with low cost and stable performance. By utilizing the characteristics of small volume, good stability and easiness in marking of the nano antibody, the nano antibody can be applied to rapid detection of pathogenic microorganisms, such as preparation of diagnostic test strips, reagents, kits and the like; the method can also be applied to basic research and tool development, such as molecular probes, separation and purification kits, construction of targeted therapy molecular core elements and the like; the early-stage and accurate screening and identification of the drug-resistant gram-negative bacteria for producing the KPC-2 type carbapenemase are realized, and the clinical precise medication and infection control are guided.

The present application relates to the technical field of medicine, in particular to the application of meropenem or aztreonam combined with nalidixic acid in the preparation of antibacterial drugs. The checkerboard dilution method minimum inhibitory concentration test, dynamic time-kill curve and galleria mellonella animal test prove that nalidixic acid can enhance the antibacterial activity of meropenem or aztreonam against carbapenem-resistant klebsiella pneumoniae, reduce the minimum inhibitory concentration of meropenem or aztreonam against carbapenem-resistant klebsiella pneumoniae, and when meropenem or aztreonam is combined with nalidixic acid, the combination shows significant synergistic antibacterial effect in vitro and in vivo against carbapenem-resistant klebsiella pneumoniae. Meropenem combined with nalidixic acid has synergistic antibacterial effect against OXA-48, NDM, KPC, IMP, VIM-producing carbapenem-resistant klebsiella pneumoniae; aztreonam combined with nalidixic acid has synergistic antibacterial effect against KPC-producing carbapenem-resistant klebsiella pneumoniae.

Multi-drug resistant (MDR) bacteria potentially pose a significant risk to people in the United States and all over the world; at the moment, the risk is the greatest where antibiotics are most commonly taken. The most notable MDR organisms are Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus faecium (VRE) and Carbapenem-resistant Pseudomonas aeruginosa. All three are associated with nosocomial infections. Embodiments of the present invention are directed to marine microorganism fractions and products for treating multi-drug resistant bacterial infections.

The invention discloses a screening method and application of a carbapenem pneumonia resistant traditional Chinese medicine inhibitor, and belongs to the technical field of biological medicine. The carbapenem-resistant klebsiella pneumoniae inhibitor high-throughput screening system is constructed on the basis of the carbapenem enzyme activity detection fluorescent probe, and the carbapenem enzyme inhibition component in the white mulberry root bark is successfully screened as the phellinus igniarius ketone G. When the inhibitor is combined with meropenem for use, metabolism of carbapenem-resistant klebsiella pneumoniae on meropenem can be remarkably inhibited, the inhibition efficiency of meropenem on strains is greatly improved, and an efficient combined medication scheme with application value is provided for clinically resisting carbapenem-resistant klebsiella pneumoniae infection.

The application relates to application of an antibacterial peptide KP4 in preparation of a medicine for resisting infection of carbapenem-resistant Klebsiella pneumoniae, and belongs to the technical field of medicines. The application provides an antibacterial peptide, and the amino acid sequence of the antibacterial peptide is shown in any one of SEQ ID NO: 1-10. Ten antibacterial peptides with the amino acid sequences shown in SEQ ID NO: 1-10 are constructed, and are respectively named as KP1, KP3, KP4, KP7, KP8, KP9, KP10, KP17, KP18 and KP19. The antibacterial peptides have certain inhibiting effects on the carbapenem-resistant Klebsiella pneumoniae, and the antibacterial peptide KP4 has the strongest inhibiting effect on the carbapenem-resistant Klebsiella pneumoniae.

This invention discloses a recombinant lysozyme derived from the myxomycete *Leptospora*, a species of myxomycete, and its preparation method and applications, relating to the field of biotechnology. The amino acid sequence of this recombinant lysozyme is shown in SEQ ID NO.1. This invention screened and obtained a novel lysozyme from *Leptospora*. Unlike traditional lysozymes that prefer Gram-positive bacteria, this lysozyme exhibits highly efficient antibacterial activity against Gram-negative bacteria such as *Escherichia coli* and *Pseudomonas aeruginosa*, and is equally effective against multidrug-resistant and carbapenem-resistant strains. This lysozyme maintains high enzyme activity at 20-60℃ and exhibits excellent stability at pH 7.0-9.0. 2+ It can significantly activate enzyme activity and has good industrial compatibility. Overall, this enzyme overcomes the bottlenecks of traditional lysozymes, such as narrow antibacterial spectrum and weak efficacy against Gram-negative bacteria, and has broad application prospects in fields such as pharmaceutical antibacterial, food preservation, and animal disease prevention.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an antibacterial peptide KP5 in preparation of a medicine for treating carbapenem-resistant acinetobacter baumannii infection. The invention finds that the antibacterial peptide KP5 with the amino acid sequence shown as SEQ ID NO: 1 has obvious inhibitory activity on carbapenem-resistant acinetobacter baumannii for the first time, so that a brand new effective treatment means can be provided for clinically treating infection (especially acute abdominal infection) caused by drug-resistant bacteria. Moreover, the invention further finds that the antibacterial peptide KP5 and the acinetobacter baumannii infection resisting drug sulbactam can generate a synergistic effect when being used together under a specific concentration, and the synergistic effect can obviously enhance the antibacterial effect on carbapenem-resistant acinetobacter baumannii; an important basis is provided for optimizing a treatment scheme for resisting carbapenem acinetobacter baumannii infection.

The application provides a combined drug for resisting klebsiella pneumoniae and application, and the combined drug for resisting klebsiella pneumoniae comprises a macrolide compound and a carbapenem antibiotic; the structural formula of the macrolide compound is shown in the following formula 1. The new macrolide compound found by the application can be synergized with imipenem, and the minimum inhibitory concentration of carbapenem-resistant klebsiella pneumoniae to imipenem can be significantly reduced to 0.78 μg / mL. In the synergistic concentration range, the macrolide compound shows good safety in vitro, and does not show cytotoxicity or hemolytic activity. Formula 1