Isoalantolactone restores the sensitivity of gram-negative Enterobacteriaceae carrying MCR-1 to carbapenems. 2020

Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China.

Polymyxin B has been re-applied to the clinic as the final choice for the treatment of multidrug-resistant gram-negative pathogenic infections, but the use of polymyxin B has been re-assessed because of the emergence and spread of the plasmid-mediated mcr-1 gene. The purpose of this study was to search for an MCR inhibitor synergistically acting with polymyxin to treat the infection caused by this pathogen. In this study, we used the broth microdilution checkerboard method to evaluate the synergistic effect of isoalantolactone (IAL) and polymyxin B on mcr-1-positive Enterobacteriaceae. Growth curve analysis, time-killing assays and a combined disc test were used to further verify the efficacy of the combined drug. Colonization of the thigh muscle in mice, survival experiments and lung tissue section observations was used to determine the effect of synergy in vivo after Klebsiella pneumoniae and Escherichia coli infection. We screened a natural compound, IAL, which can enhance the sensitivity of polymyxin B to mcr-1-positive Enterobacteriaceae. The results showed that the combined use of polymyxin B and IAL has a synergistic effect on mcr-1-positive Enterobacteriaceae, such as K pneumoniae and E coli, not only in vitro but also in vivo. Our results indicate that IAL is a natural compound with broad application prospects that can prolong the service life of polymyxin B and make outstanding contributions to the treatment of gram-negative Enterobacteriaceae infections resistant to polymyxin B.

UI MeSH Term Description Entries
D007710 Klebsiella Infections Infections with bacteria of the genus KLEBSIELLA. Infections, Klebsiella,Infection, Klebsiella,Klebsiella Infection
D007711 Klebsiella pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Bacillus pneumoniae,Bacterium pneumoniae crouposae,Hyalococcus pneumoniae,Klebsiella pneumoniae aerogenes,Klebsiella rhinoscleromatis
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D011112 Polymyxin B A mixture of polymyxins B1 and B2, obtained from BACILLUS POLYMYXA strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for treatment of infections with gram-negative bacteria, but may be neurotoxic and nephrotoxic. Aerosporin,Polymyxin B Sulfate
D004755 Enterobacteriaceae A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock. Coliform Bacilli,Enterobacteria,Ewingella,Leclercia,Paracolobactrum,Sodalis
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D004927 Escherichia coli Infections Infections with bacteria of the species ESCHERICHIA COLI. E coli Infections,E. coli Infection,Infections, E coli,Infections, Escherichia coli,E coli Infection,E. coli Infections,Escherichia coli Infection,Infection, E coli,Infection, E. coli,Infection, Escherichia coli
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
August 2023, Phytomedicine : international journal of phytotherapy and phytopharmacology,
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
February 2019, Journal of clinical medicine,
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
April 2017, The Journal of antimicrobial chemotherapy,
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
November 2010, Medecine sciences : M/S,
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
June 2023, Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology],
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
May 2024, International journal of antimicrobial agents,
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
September 2016, Emerging infectious diseases,
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
December 2020, JNMA; journal of the Nepal Medical Association,
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
January 2023, Research (Washington, D.C.),
Na Lu, and Qianghua Lv, and Xiaodi Sun, and Yonglin Zhou, and Yan Guo, and Jiazhang Qiu, and Peng Zhang, and Jianfeng Wang
December 2022, Emerging microbes & infections,
Copied contents to your clipboard!