137 results about "Carbapenem" patented technology

The invention discloses development, preparation and application of a carbapenemase immunochromatography kit, and belongs to the technical field of biological medicines. According to comparison of amino acid sequences of five common carbapenemase variants of KPC, IMP, NDM, VIM and OXA48 types, the immunogen is prepared from conserved epitope sequences obtained respectively. A mouse is immunized, and a specific antibody pair which is strong in affinity and can be combined with multiple variants is obtained through multi-platform screening. On the basis, the carbapenemase quintuplet detection kit is developed by utilizing an immunochromatography method, has the advantages of high sensitivity, good specificity, capability of covering various drug-resistant variants, capability of detecting multiple targets at one time and rapidness and convenience in detection, and provides important help for clinical auxiliary diagnosis and medication guidance.

The invention discloses preparation of an antibody capable of detecting multi-subtype KPC and application of a kit of the antibody, and belongs to the field of biological medicine. According to the kit for detecting the common subtypes of KPC and the application of the kit, the mouse antibodies are prepared through immunization of conserved antigen epitopes of all the subtypes of KPC, in-vitro screening and pairing are carried out in multiple modes, then an antibody pair which is good in specificity and high in affinity and can be combined with multiple subtypes is obtained, the titer of the two antibodies can reach one million or above, and the kit is high in specificity, good in affinity and capable of being used for detecting the common subtypes of KPC. Amino acid sequences of a heavy chain variable region and a light chain variable region are obtained through sequencing, and rapid and stable expression can be realized after recombination. The product for detecting the carbapenem KPC is developed on the basis of an immunochromatography platform, and the kit has the advantages of high sensitivity, good specificity, good stability, capability of covering most epidemic KPC subtypes and rapidness and convenience in detection, and provides important help for clinical auxiliary diagnosis and medication guidance.

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 relates to the technical field of high-throughput targeted sequencing, in particular to a primer group for detecting important drug-resistant genes and virulence genes of multi-drug-resistant pathogenic bacteria and application of the primer group. Specifically, the kit comprises detection primers for multiple drug-resistant bacteria such as third-generation cephalosporin drug-resistant enterobacteriaceae bacteria, carbapenem drug-resistant enterobacteriaceae bacteria, carbapenem drug-resistant acinetobacter baumannii, rifampicin drug-resistant mycobacterium tuberculosis and the like. The method has the technical advantages of rapidness, high efficiency, strong targeting property, strong specificity and the like, is suitable for epidemic and difference analysis of various important drug-resistant genes and virulence genes carried by metagenome samples of various environments or disease materials and the like, evaluates the risk of related environments on the basis, and can further guide prevention and clinical treatment medication.

The invention discloses a carbapenem drug resistance gene detection reagent or kit, the detection reagent comprises a PCR detection liquid, the PCR detection liquid comprises upstream and downstream primer sequences and probe sequences of target genes, and the target genes are KPC, OXA-23, NDM, VIM and IMP. The invention also discloses application of the reagent or the kit. The reagent / kit provided by the invention has simple components, only comprises a PCR detection liquid and negative and positive quality control, can obtain detection results of five major carbapenem drug resistance genes, namely KPC, OXA-23, NDM, VIM and IMP, within about 50 minutes only once, and is simple and convenient to operate, low in detection cost, short in detection time and high in sensitivity. In addition, the lowest detectable concentration of detection of carbapenem drug resistance genes KPC, OXA-23, NDM, VIM and IMP is 10 copy / mL, and the sensitivity is high.

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 designs a carbapenem drug-resistant gene nucleic acid fluorescent PCR method detection kit and application thereof, the kit uses Taqman fluorescent probe multiple amplification technology to detect carbapenem drug-resistant genes, the kit comprises a nucleic acid reaction liquid Mix1 and a nucleic acid reaction liquid Mix2, the nucleic acid reaction liquid Mix1 is used for detecting drug-resistant genes IMP, NDM and OXA48, the nucleic acid reaction liquid Mix2 is used for detecting drug-resistant genes IMP, NDM and OXA48, and the nucleic acid reaction liquid Mix2 is used for detecting drug-resistant genes IMP, NDM and OXA48. The nucleic acid reaction liquid Mix2 is used for detecting drug resistance genes VIM, KPC and OXA23. The method is high in detection specificity, and the detection result is visual and easy to interpret. Clinical doctors are assisted to judge respiratory tract pathogen infection more comprehensively and more accurately. The kit covers six carbapenem drug resistance genes, is more comprehensive and accurate in detection, and is high in specificity and sensitivity. Meanwhile, multiple sample types can be detected, a sputum sample, an excrement sample and a rectum swab sample are detected through paramagnetic particle extraction, and pure bacterial colonies are directly detected without extraction.

There is provided a method of at least partially inhibiting the function of Klebsiella pneumoniae carbapenemase-2 (KPC-2) or a variant thereof, the method comprising reacting said KPC-2 with a compound selected from the group consisting of 5-chloro-1, 3-dihydro-1-hydroxy-2, 1-benzoxaborolane, 5-fluoro-1, 3-dihydro-1-hydroxy-2, 1-benzoxaborolane, 5-fluoro-1, 3-dihydro-1-hydroxy-2, 1-benzoxaborolane, 5-fluoro-1, 3-dihydro-1-hydroxy-2, 1-benzoxaborolane, 5-chloro-1, 3-dihydro-1-hydroxy-2, 1-benzoxaborolane, 5-chloro-1, 3-dihydro-1-hydroxy-2, 1- The present invention relates to a method for contacting a beta-lactam antibiotic-resistant bacterium with a benzoxaborolane selected from the group consisting of 1, 1-benzoxaborolane and mixtures thereof, which can be used to treat an infection with a beta-lactam antibiotic-resistant bacterium in a subject.

The invention relates to an antibacterial peptide and application thereof. The amino acid sequence of the antibacterial peptide is as shown in SEQ ID No. 1. The antibacterial peptide has excellent broad-spectrum antibacterial activity, for example, the antibacterial peptide has antibacterial activity on bacteria of the genus Staphylococcus (Staphylococcus), the genus Acinetobacter (Acinetobacter) and the genus Bacillus (Bacillus). Under the background that the global bacterial drug resistance problem is increasingly severe and traditional antibiotics gradually lose efficacy on multi-drug-resistant bacteria, a new treatment means is provided for treating bacteria such as methicillin-resistant staphylococcus aureus, carbapenem-resistant acinetobacter baumannii and bacillus subtilis which bring huge threats to public health. And a new possibility is provided for solving the problem that no medicine can be used clinically.

The present invention relates to the pharmaceutical field, and provides a boric acid β-lactamase inhibitor or a use thereof. The boric acid β-lactamase inhibitor is a compound shown in formula (I), or an optical isomer or a pharmaceutically acceptable salt thereof: formula (I). The ultra-broad-spectrum boric acid β-lactamase inhibitor of the present invention has an inhibition effect on A, B, C, and D enzymes, and carbapenem drug-resistant bacteria such as Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Acinetobacter baumannii, and Pseudomonas aeruginosa.

The present invention relates to a composition for preventing or treating gram-negative bacterial infections, the composition comprising T. ni cecropin. According to an aspect of the present invention, the peptide T. ni cecropin has the excellent effects of reducing liver and kidney toxicity values, inflammatory cytokine production, and endotoxins and inhibiting inflammatory cell infiltration in animal models infected with LPS-infected endotoxemia and Carbapenem-resistant Acinetobacter baumannii and can thus be effectively used for preventing or treating bacterial infections (e.g., gram-negative bacterial infections), sepsis, or inflammatory diseases.

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 chlorogenic acid in preparation of a product for resisting carbapenem-resistant klebsiella pneumoniae, and belongs to the technical field of medicines. It is verified that chlorogenic acid has a good in-vitro killing effect on carbapenem-resistant klebsiella pneumonia, growth of the carbapenem-resistant klebsiella pneumonia can be inhibited, the minimum inhibitory concentration is 20 mg / mL, and a biological membrane of the carbapenem-resistant klebsiella pneumonia can be effectively destroyed. The invention provides the inhibition effect of chlorogenic acid on carbapenem-resistant klebsiella pneumoniae, and the chlorogenic acid has wide application value in the fields of medicines and the like.

The invention discloses a klebsiella pneumoniae bacteriophage vBKpnPGZMUVR401 and application thereof, and relates to the technical field of biology. The klebsiella pneumoniae bacteriophage vBKpnPGZMUVR401 is preserved in Guangdong Microbial Culture Collection Center on October 14, 2024, the preservation address is the 5th floor of the building 59, No.100 Courtyard, Xianlie Middle Road, Guangzhou, and the preservation number is GDMCC No: 65265-B1. The bacteriophage is stable in titer under the environment that the pH is 4-10 and the temperature is 4-50 DEG C, the titer can be up to 1011 pfu / mL or above, and the bacteriophage can split klebsiella pneumoniae and particularly can strongly split carbapenem-resistant klebsiella pneumoniae (CRKP). The invention provides a technical support for developing a novel antibacterial drug and an antibacterial scheme for inhibiting klebsiella pneumoniae, and has a good application prospect.

The present application relates to the field of biotechnology, in particular to a carbapenem-resistant escherichia coli phage and application thereof.A new escherichia coli phage vB_EOP_Se009 is isolated and purified, and the phage has good sterilization effect on carbapenem-resistant escherichia coli.The phage has strong tolerance to temperature and pH, is high in specificity and stability, can effectively solve the problem that carbapenem-resistant escherichia coli is resistant to multiple antibiotics, and provides an experimental basis for developing a preparation for preventing or treating carbapenem-resistant escherichia coli infection in clinic, and has great clinical application potential.

The present application belongs to the technical field of artificial intelligence assisted drug screening, and particularly relates to a method for screening active molecules against carbapenem-resistant enterobacteriaceae based on a LightGBM algorithm, a medium and an apparatus. The method constructs a LightGBM integrated learning framework, fuses ADME rules optimized for the outer membrane barrier characteristics of gram-negative bacteria and multi-target molecule docking verification, effectively solves the problem of data imbalance caused by the scarcity of active samples and the huge compound library, and significantly improves the hit rate of screening. The present application also provides a computer readable storage medium and an electronic device. By storing and executing the above program, the present application can quickly and standardizedly identify anti-CRE candidate molecules from a large number of compounds, greatly reducing the computing power cost and time cycle of new drug research and development. The present application is designed to overcome the bottleneck of gram-negative bacterial outer membrane permeation, and provides an efficient, accurate and intelligent screening tool for combating CRE super-bacterial infections.

The invention discloses an antibody as well as a preparation method and application thereof. The antibody has good binding activity with OXA-23 type carbapenem enzyme, and can reduce the carbapenem drug resistance level of the acinetobacter baumannii, so that the clinical use concentration of meropenem is reduced, and the treatment effect of meropenem on the acinetobacter baumannii is improved. In addition, the antibody disclosed by the invention can also inhibit OXA-23 protein secreted by bacteria, prevent the bacteria from hydrolyzing carbapenem antibiotics, increase the concentration of antibiotics in a medication part, and facilitate the removal of mixed infection with acinetobacter baumannii. The invention provides a new strategy for treating acinetobacter baumannii infection, and the application prospect is wide.

This invention relates to compounds of formula (I) and methods of treatment using the compounds. The compounds of the invention can be used in combination with antibacterial agents to treat bacterial infections. More specifically, the compounds of formula (I) can be used in combination with a class of antibacterial agents known as carbapenems. The novel compounds of the present invention are enzyme inhibitors and more particularly are metallo-β-lactamase inhibitors.

The invention provides a broad-spectrum bacteriophage capable of efficiently splitting carbapenem-resistant klebsiella pneumoniae and application of the broad-spectrum bacteriophage, and belongs to the technical field of biological medicines. The bacteriophage is named as P146043, the host spectrum of the bacteriophage is wide, the bacteriophage can be used for CRKP strains of four ST genotypes and eight KL capsule types, and the antibacterial effect is good; meanwhile, good acid and alkali resistance and temperature stability are achieved; and the bacteriophage has a synergistic antibacterial effect with other bacteriophages, so that the antibacterial time can be prolonged. The P146043 provides an effective method and a new prevention and treatment thought for prevention and treatment of CRKP infectious disease infection, and has a good application prospect.

The invention relates to the field of bacterium detection, in particular to a reagent and a method for detecting carbapenemase type bacteria in enterobacter bacteria. According to the reagent and the method for detecting the carbapenemase type bacteria in the enterobacter bacteria, provided by the invention, the ethylenediaminetetraacetic acid compound and the triaminophenylboronic acid are matched, and the ratio of the ethylenediaminetetraacetic acid compound and the triaminophenylboronic acid is limited, so that strains which generate A-type carbapenemase, B-type carbapenemase and simultaneously generate A-type carbapenemase and B-type carbapenemase are identified; the invention provides a method capable of simply detecting and distinguishing carbapenemase in enterobacter bacteria, not only can realize typing of carbapenemase, but also is simple to operate, easy in result reading and low in cost, and is very suitable for clinical detection of enterobacter carbapenemase phenotypes. In addition, the invention further provides a bacterium sampler used in the method for detecting carbapenemase type bacteria in enterobacter bacteria, and the bacterium sampler not only can be used for carrying out high-temperature sterilization treatment on the scribing rod by utilizing a ceramic heat preservation cabin and a windproof lighter, but also can be used for carrying out sterilization treatment on airflow.

This invention relates to the synthesis of compounds that can be used to treat bacterial infections in combination with other antibacterial agents, and more specifically in combination with a class of antibacterial agents known as carbapenems. The compounds resulting from the novel methods of the present invention are enzyme inhibitors and more particularly are metallo-β-lactamase inhibitors.

The present application relates to a kind of targeting bacterial UDP-N-acetylglucosamine enolpyruvate transaminase antibacterial compound and its application, the antibacterial compound is S-(4-chlorobenzyl) chloro isothiourea, its chemical structure is as shown in formula I: I;Or its pharmaceutically acceptable salt, stereoisomer, solvate, crystal form, isotopically labeled or prodrug.The antibacterial compound of the present application can effectively inhibit the growth of klebsiella pneumoniae, including carbapenem-resistant klebsiella pneumoniae and high virulence klebsiella pneumoniae;It also has good bacteriostatic effect on escherichia coli and pseudomonas aeruginosa;It is expected to be applied to the clinical treatment of infection caused by drug-resistant klebsiella pneumoniae and high virulence klebsiella pneumoniae and other pathogenic bacteria, and has important clinical significance and social benefits.

The application provides a drug delivery system for targeted treatment of inflammatory diseases and a preparation method and application thereof, and belongs to the technical field of biological drugs. The drug delivery system for targeted treatment of inflammatory diseases is M2 type macrophages phagocytizing drug-loaded nanoparticles, wherein the drug-loaded nanoparticles comprise a biodegradable high molecular material for coating drugs. The drug delivery system prepared by the application realizes lung targeted delivery through the natural inflammatory chemotaxis characteristics of M2 type macrophages, and in combination with the drug slow-release effect of the drug-loaded nanoparticles, the drug targeting and availability are significantly improved, so that the drug efficacy is improved, the biological safety is good, and a new effective means is provided for the clinical treatment of various inflammatory diseases including carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia.

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 invention belongs to the technical field of gene detection, and particularly relates to a carbapenem drug resistance gene detection device and method.The carbapenem drug resistance gene detection device comprises a detector, a detection cavity is formed in the detector, a detection unit is arranged in the detection cavity, and the detection unit comprises a pneumatic control module, an optical detection module and a constant temperature module; a sealing cover for sealing the detection cavity is arranged on the top surface of the detector; a micro-fluidic chip is placed on a suction cup, the micro-fluidic chip is pressed to be adsorbed on the suction cup, then a sealing cover is closed, an electric telescopic rod moves downwards, a first spring pushes a connecting plate, the connecting plate drives the suction cup to move downwards, and the suction cup drives the chip to move downwards; when the micro-fluidic chip is placed in the groove, the bottom surface of the chip is in contact with the inner wall of the groove, and then the electric telescopic rod is closed, so that the micro-fluidic chip is fixed in the groove, and the micro-fluidic chips of different models and sizes can be fixed through the suction cup.

Compositions and methods are provided for treating bacterial infections, including those that are challenging to treat by conventional medications, such as hospital acquired bacterial pneumonia (HABP), ventilator associated bacterial pneumonia (VABP), and bacteremia, caused by carbapenem-resistant bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa.

The invention discloses a carbapenem drug resistance marker screening method and system based on a cross-species compressed Debrueine diagram and a medium. The method comprises the following steps: starting from whole genome sequencing data of gram-negative bacteria belonging to different species and carbapenem drug phenotypes of the gram-negative bacteria, constructing a compressed Debrueine graph based on cross-species joint data, and taking existence / deletion of nodes in the graph as unified genetic variation characteristics. Performing correlation analysis on the nodes and the drug resistance phenotypes by using a linear hybrid model to obtain a candidate node set related to the phenotypes; k-mer is extracted based on the candidate node sequence, and secondary statistical screening is completed in combination with chi-square test and mutual information; and finally determining a group of carbapenem drug-resistant genetic markers which can be applicable across species through a hierarchical feature selection strategy of random forest and XGBoost. Efficient dimension reduction of large-scale cross-species genome data, cross-species consistent variation representation and high-interpretability marker screening are achieved.

The present invention discloses a strain of Bacillus Velez CB6 and the antimicrobial protein produced and its application, belonging to the field of microbial application technology. The deposit number of the Bacillus Velez CB6 is CGMCC NO.30515. The strain has a good antagonistic effect on Gram-negative bacteria such as multidrug-resistant Escherichia coli. The antimicrobial protein CB6-E prepared by fermentation of the strain shows good antimicrobial activity against a variety of Gram-negative bacteria, and has good safety for a variety of animals. CB6-E has a good therapeutic effect on mice and wax moths infected with polymyxin-resistant and carbapenem-resistant Escherichia coli. The antimicrobial protein CB6-E prepared by fermentation of Bacillus Velez CB6 of the present invention is expected to enrich the current existing antimicrobial drug library and provide new hope for the treatment of multidrug-resistant Gram-negative bacterial infections.

The invention belongs to the technical field of antibacterial drugs, and particularly relates to a benzo five-membered ring boric acid-3-methyl alkenyl acid compound as well as a preparation method and application thereof. The invention provides a benzo five-membered ring boric acid-3-methyl alkenyl acid compound as shown in a formula I. The benzo five-membered ring boric acid-3-methyl alkenyl acid compound has good and broad-spectrum inhibitory activity on metal beta-lactamase and / or serine beta-lactamase, has excellent antibacterial activity on various drug-resistant bacteria, and can reverse drug resistance of carbapenem drug-resistant bacteria. Therefore, the compound disclosed by the invention has a wide application prospect in preparation of inhibitors of metal beta-lactamase and / or serine beta-lactamase and drugs for reversing drug resistance of carbapenem drug-resistant bacteria. # imgabs0 #