Hui Zuo, Yo Sugawara, Kohei Kondo, Shizuo Kayama, Sayoko Kawakami, Kohei Uechi, Ami Nakano, Koji Yahara, Motoyuki Sugai
{"title":"Emergence of an IncX3 plasmid co-harbouring the carbapenemase genes <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>OXA-181</sub>.","authors":"Hui Zuo, Yo Sugawara, Kohei Kondo, Shizuo Kayama, Sayoko Kawakami, Kohei Uechi, Ami Nakano, Koji Yahara, Motoyuki Sugai","doi":"10.1093/jacamr/dlae073","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The spread of transmissible plasmids with carbapenemase genes has contributed to a global increase in carbapenemase-producing Enterobacterales over the past two decades, with <i>bla</i><sub>NDM</sub> and <i>bla</i><sub>OXA</sub> among the most prevalent carbapenemase genes.</p><p><strong>Objectives: </strong>To characterize an <i>Escherichia coli</i> isolate co-carrying <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>OXA-181</sub> (JBEHAAB-19-0176) that was isolated in the Japan Antimicrobial Resistant Bacterial Surveillance in 2019-20, and to evaluate the functional advantage of carrying both genes as opposed to only one.</p><p><strong>Methods: </strong>The whole-genome sequence of the isolate was determined using long- and short-read sequencing. Growth assay and co-culture experiments were performed for phenotypic characterization in the presence of different β-lactam antibiotics.</p><p><strong>Results: </strong>WGS analysis showed that <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>OXA-181</sub> were carried by the same IncX3 plasmid, pJBEHAAB-19-0176_NDM-OXA. Genetic characterization of the plasmid suggested that the plasmid emerged through the formation of a co-integrate and resolution of two typical IncX3 plasmids harbouring <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>OXA-181</sub>, which involved two recombination events at the IS<i>3000</i> and IS<i>26</i> sequences. When cultured in the presence of piperacillin or cefpodoxime, the growth rate of the transformant co-harbouring <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>OXA-181</sub> was significantly higher than the transformant with only <i>bla</i><sub>NDM-5</sub>. Furthermore, in co-culture where the two <i>bla</i><sub>NDM-5</sub>-harbouring transformants were allowed to compete directly, the strain additionally harbouring <i>bla</i><sub>OXA-181</sub> showed a marked growth advantage.</p><p><strong>Conclusions: </strong>The additional carriage of <i>bla</i><sub>OXA-181</sub> confers a selective advantage to bacteria in the presence of piperacillin and cefpodoxime. These findings may explain the current epidemiology of carbapenemase-producing Enterobacterales, in which bacteria carrying both <i>bla</i><sub>NDM-5</sub> and <i>bla</i><sub>OXA-48</sub>-like genes have emerged independently worldwide.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089413/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAC-Antimicrobial Resistance","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jacamr/dlae073","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The spread of transmissible plasmids with carbapenemase genes has contributed to a global increase in carbapenemase-producing Enterobacterales over the past two decades, with blaNDM and blaOXA among the most prevalent carbapenemase genes.
Objectives: To characterize an Escherichia coli isolate co-carrying blaNDM-5 and blaOXA-181 (JBEHAAB-19-0176) that was isolated in the Japan Antimicrobial Resistant Bacterial Surveillance in 2019-20, and to evaluate the functional advantage of carrying both genes as opposed to only one.
Methods: The whole-genome sequence of the isolate was determined using long- and short-read sequencing. Growth assay and co-culture experiments were performed for phenotypic characterization in the presence of different β-lactam antibiotics.
Results: WGS analysis showed that blaNDM-5 and blaOXA-181 were carried by the same IncX3 plasmid, pJBEHAAB-19-0176_NDM-OXA. Genetic characterization of the plasmid suggested that the plasmid emerged through the formation of a co-integrate and resolution of two typical IncX3 plasmids harbouring blaNDM-5 and blaOXA-181, which involved two recombination events at the IS3000 and IS26 sequences. When cultured in the presence of piperacillin or cefpodoxime, the growth rate of the transformant co-harbouring blaNDM-5 and blaOXA-181 was significantly higher than the transformant with only blaNDM-5. Furthermore, in co-culture where the two blaNDM-5-harbouring transformants were allowed to compete directly, the strain additionally harbouring blaOXA-181 showed a marked growth advantage.
Conclusions: The additional carriage of blaOXA-181 confers a selective advantage to bacteria in the presence of piperacillin and cefpodoxime. These findings may explain the current epidemiology of carbapenemase-producing Enterobacterales, in which bacteria carrying both blaNDM-5 and blaOXA-48-like genes have emerged independently worldwide.