{"title":"研究blaNDM在抗生素选择性环境中的分子传播动力学。","authors":"Shashi Kumari, Lekshmi Narendrakumar, Meenal Chawla, Sanjib Das, Hemanta Koley, Bhabatosh Das","doi":"10.1128/jb.00133-25","DOIUrl":null,"url":null,"abstract":"<p><p>Carbapenem resistance mediated by <i>bla</i><sub>NDM</sub>-encoded metallo-beta-lactamases is often linked to IS<i>Aba125</i>, an insertion sequence from the IS<i>30</i> family, which is widely distributed among critical and high-priority bacterial pathogens. The rapid dissemination of IS<i>Aba125</i>-linked <i>bla</i><sub>NDM</sub> in both nosocomial and community-acquired infections presents a serious challenge to healthcare systems and pharmaceutical industries. Despite the urgency of this issue, the factors driving <i>bla</i><sub>NDM</sub> spread and the molecular mechanisms governing IS<i>Aba125</i> mobility remain poorly understood. In this study, we engineered the genomes of <i>Vibrio cholerae</i> and <i>Escherichia coli</i> to investigate the mobility of <i>bla</i><sub>NDM</sub> under controlled conditions both with and without the genetically linked IS<i>Aba125</i>. We also examined the transmission efficiency and the stability of <i>bla</i><sub>NDM</sub> in environments with and without sublethal antibiotic concentrations. Our <i>in vitro</i> findings were validated in a rabbit ileal loop model. The results revealed that antibiotic pressure significantly influences the mobility of <i>bla</i><sub>NDM</sub>, shedding light on the molecular dynamics of its transmission. These insights are crucial for developing strategies to curb the spread of <i>bla</i><sub>NDM</sub> and mitigate the growing threat of carbapenem resistance in bacterial pathogens.IMPORTANCEInsertion sequences are the simplest form of mobile genetic elements that play a critical role in the adaptation of bacteria, allowing them to rapidly acquire new traits like resistance genes that enhance their survival. IS<i>Aba125</i> is one such insertion sequence that facilitates the spread of <i>bla</i><sub>NDM</sub>, contributing to the global challenge of carbapenem resistance. In this study, we developed reporter strains that could be used as a valuable tool for investigating the dynamics of IS<i>Aba125-</i>linked <i>bla</i><sub>NDM</sub><i>sh-ble</i> and evaluated the transposition frequency of IS<i>Aba125-</i>linked <i>bla</i><sub>NDM</sub><i>sh-ble</i> in the presence and absence of sublethal concentration of antibiotics. Our results demonstrated that IS<i>Aba125</i> enhances the spread of <i>bla</i><sub>NDM</sub><i>sh-ble</i> under sublethal concentration of antibiotics that induces SOS response.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0013325"},"PeriodicalIF":3.0000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445084/pdf/","citationCount":"0","resultStr":"{\"title\":\"Investigating the molecular transmission dynamics of <i>bla</i><sub>NDM</sub> in antibiotic-selective environments.\",\"authors\":\"Shashi Kumari, Lekshmi Narendrakumar, Meenal Chawla, Sanjib Das, Hemanta Koley, Bhabatosh Das\",\"doi\":\"10.1128/jb.00133-25\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Carbapenem resistance mediated by <i>bla</i><sub>NDM</sub>-encoded metallo-beta-lactamases is often linked to IS<i>Aba125</i>, an insertion sequence from the IS<i>30</i> family, which is widely distributed among critical and high-priority bacterial pathogens. The rapid dissemination of IS<i>Aba125</i>-linked <i>bla</i><sub>NDM</sub> in both nosocomial and community-acquired infections presents a serious challenge to healthcare systems and pharmaceutical industries. Despite the urgency of this issue, the factors driving <i>bla</i><sub>NDM</sub> spread and the molecular mechanisms governing IS<i>Aba125</i> mobility remain poorly understood. In this study, we engineered the genomes of <i>Vibrio cholerae</i> and <i>Escherichia coli</i> to investigate the mobility of <i>bla</i><sub>NDM</sub> under controlled conditions both with and without the genetically linked IS<i>Aba125</i>. We also examined the transmission efficiency and the stability of <i>bla</i><sub>NDM</sub> in environments with and without sublethal antibiotic concentrations. Our <i>in vitro</i> findings were validated in a rabbit ileal loop model. The results revealed that antibiotic pressure significantly influences the mobility of <i>bla</i><sub>NDM</sub>, shedding light on the molecular dynamics of its transmission. These insights are crucial for developing strategies to curb the spread of <i>bla</i><sub>NDM</sub> and mitigate the growing threat of carbapenem resistance in bacterial pathogens.IMPORTANCEInsertion sequences are the simplest form of mobile genetic elements that play a critical role in the adaptation of bacteria, allowing them to rapidly acquire new traits like resistance genes that enhance their survival. IS<i>Aba125</i> is one such insertion sequence that facilitates the spread of <i>bla</i><sub>NDM</sub>, contributing to the global challenge of carbapenem resistance. In this study, we developed reporter strains that could be used as a valuable tool for investigating the dynamics of IS<i>Aba125-</i>linked <i>bla</i><sub>NDM</sub><i>sh-ble</i> and evaluated the transposition frequency of IS<i>Aba125-</i>linked <i>bla</i><sub>NDM</sub><i>sh-ble</i> in the presence and absence of sublethal concentration of antibiotics. Our results demonstrated that IS<i>Aba125</i> enhances the spread of <i>bla</i><sub>NDM</sub><i>sh-ble</i> under sublethal concentration of antibiotics that induces SOS response.</p>\",\"PeriodicalId\":15107,\"journal\":{\"name\":\"Journal of Bacteriology\",\"volume\":\" \",\"pages\":\"e0013325\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445084/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Bacteriology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1128/jb.00133-25\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bacteriology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/jb.00133-25","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Investigating the molecular transmission dynamics of blaNDM in antibiotic-selective environments.
Carbapenem resistance mediated by blaNDM-encoded metallo-beta-lactamases is often linked to ISAba125, an insertion sequence from the IS30 family, which is widely distributed among critical and high-priority bacterial pathogens. The rapid dissemination of ISAba125-linked blaNDM in both nosocomial and community-acquired infections presents a serious challenge to healthcare systems and pharmaceutical industries. Despite the urgency of this issue, the factors driving blaNDM spread and the molecular mechanisms governing ISAba125 mobility remain poorly understood. In this study, we engineered the genomes of Vibrio cholerae and Escherichia coli to investigate the mobility of blaNDM under controlled conditions both with and without the genetically linked ISAba125. We also examined the transmission efficiency and the stability of blaNDM in environments with and without sublethal antibiotic concentrations. Our in vitro findings were validated in a rabbit ileal loop model. The results revealed that antibiotic pressure significantly influences the mobility of blaNDM, shedding light on the molecular dynamics of its transmission. These insights are crucial for developing strategies to curb the spread of blaNDM and mitigate the growing threat of carbapenem resistance in bacterial pathogens.IMPORTANCEInsertion sequences are the simplest form of mobile genetic elements that play a critical role in the adaptation of bacteria, allowing them to rapidly acquire new traits like resistance genes that enhance their survival. ISAba125 is one such insertion sequence that facilitates the spread of blaNDM, contributing to the global challenge of carbapenem resistance. In this study, we developed reporter strains that could be used as a valuable tool for investigating the dynamics of ISAba125-linked blaNDMsh-ble and evaluated the transposition frequency of ISAba125-linked blaNDMsh-ble in the presence and absence of sublethal concentration of antibiotics. Our results demonstrated that ISAba125 enhances the spread of blaNDMsh-ble under sublethal concentration of antibiotics that induces SOS response.
期刊介绍:
The Journal of Bacteriology (JB) publishes research articles that probe fundamental processes in bacteria, archaea and their viruses, and the molecular mechanisms by which they interact with each other and with their hosts and their environments.