Zixian Wang, Jingyi Guo, Gejin Lu, Jie Jing, Shiwen Sun, Yang Sun, Xue Ji, Bowen Jiang, Bing Liang, Chuanfang Zhao, Lin Zheng, Lingwei Zhu, Xuejun Guo
{"title":"猪源性大肠杆菌mcr-1与blaCTX-M的共存及头孢菌素压力下mcr-1的选择","authors":"Zixian Wang, Jingyi Guo, Gejin Lu, Jie Jing, Shiwen Sun, Yang Sun, Xue Ji, Bowen Jiang, Bing Liang, Chuanfang Zhao, Lin Zheng, Lingwei Zhu, Xuejun Guo","doi":"10.1016/j.jgar.2025.08.018","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The usage of cephalosporins (CEFs) and co-existence of extended-spectrum β-lactamase (ESBL) gene bla<sub>CTX-M</sub> in the same host may promote the prevalence of colistin (CST) resistance gene mcr-1. This study aims to investigate the underlying mechanisms how the mcr-1 and bla<sub>CTX-M</sub> demonstrate significant co-occurrence in Escherichia coli (E. coli).</p><p><strong>Methods: </strong>Conjugation assays were performed on 22 porcine-derived mcr-1-positive and bla<sub>CTX-M</sub>-positive E. coli (MCRPEC::bla<sub>CTX-M</sub><sup>+</sup>) isolates from China to assess co-transfer potential. Whole genome sequencing characterized the genetic localization and context of mcr-1 and bla<sub>CTX-M</sub>. Fitness cost and genetic stability were evaluated through growth curve and anti-microbial resistance (AMR) gene stability rates measurement. Additionally, we examined mcr-1 selection during bla<sub>CTX-M</sub> co-existence under CEFs pressure by monitoring fitness and stability variations in mcr-1.</p><p><strong>Results: </strong>Successful co-transfer of mcr-1 and bla<sub>CTX-M</sub> occurred in 36% (8/22) of isolates, demonstrating co-transfer efficiency ranging from 1.3×10<sup>-5</sup> to 1.5×10<sup>-3</sup>. Predominant plasmid combinations facilitating co-transfer were IncI2(mcr-1) + IncI1(bla<sub>CTX-M</sub>) combination. Notably, we report the first identification of bla<sub>CTX-M</sub>-positive E. coli (CTX-M-EC) carrying dual mcr-1 copies on plasmids. mcr-1 and bla<sub>CTX-M</sub> did not exhibit fitness costs in 63% (5/8) of transconjugants, with 88% (7/8) maintaining over 70% stable rate in 10 days. CEFs pressure enhanced both fitness and stability of mcr-1 in bla<sub>CTX-M</sub> co-harboring transconjugants.</p><p><strong>Conclusions: </strong>The observed high co-transfer efficiency, high stability rates, and low fitness costs of mcr-1 and bla<sub>CTX-M</sub> across distinct plasmid types and the mcr-1 selection driven by CEFs support the co-existence of mcr-1 and bla<sub>CTX-M</sub> in E. coli hosts. Our findings support a suggestion that an urgent need for coordinated antibiotic stewardship targeting both drug classes to curb multidrug-resistant bacteria spread.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Co-existence of mcr-1 and bla<sub>CTX-M</sub> from porcine-derived Escherichia coli isolated in China and selection of mcr-1 under cephalosporins pressure.\",\"authors\":\"Zixian Wang, Jingyi Guo, Gejin Lu, Jie Jing, Shiwen Sun, Yang Sun, Xue Ji, Bowen Jiang, Bing Liang, Chuanfang Zhao, Lin Zheng, Lingwei Zhu, Xuejun Guo\",\"doi\":\"10.1016/j.jgar.2025.08.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The usage of cephalosporins (CEFs) and co-existence of extended-spectrum β-lactamase (ESBL) gene bla<sub>CTX-M</sub> in the same host may promote the prevalence of colistin (CST) resistance gene mcr-1. This study aims to investigate the underlying mechanisms how the mcr-1 and bla<sub>CTX-M</sub> demonstrate significant co-occurrence in Escherichia coli (E. coli).</p><p><strong>Methods: </strong>Conjugation assays were performed on 22 porcine-derived mcr-1-positive and bla<sub>CTX-M</sub>-positive E. coli (MCRPEC::bla<sub>CTX-M</sub><sup>+</sup>) isolates from China to assess co-transfer potential. Whole genome sequencing characterized the genetic localization and context of mcr-1 and bla<sub>CTX-M</sub>. Fitness cost and genetic stability were evaluated through growth curve and anti-microbial resistance (AMR) gene stability rates measurement. Additionally, we examined mcr-1 selection during bla<sub>CTX-M</sub> co-existence under CEFs pressure by monitoring fitness and stability variations in mcr-1.</p><p><strong>Results: </strong>Successful co-transfer of mcr-1 and bla<sub>CTX-M</sub> occurred in 36% (8/22) of isolates, demonstrating co-transfer efficiency ranging from 1.3×10<sup>-5</sup> to 1.5×10<sup>-3</sup>. Predominant plasmid combinations facilitating co-transfer were IncI2(mcr-1) + IncI1(bla<sub>CTX-M</sub>) combination. Notably, we report the first identification of bla<sub>CTX-M</sub>-positive E. coli (CTX-M-EC) carrying dual mcr-1 copies on plasmids. mcr-1 and bla<sub>CTX-M</sub> did not exhibit fitness costs in 63% (5/8) of transconjugants, with 88% (7/8) maintaining over 70% stable rate in 10 days. CEFs pressure enhanced both fitness and stability of mcr-1 in bla<sub>CTX-M</sub> co-harboring transconjugants.</p><p><strong>Conclusions: </strong>The observed high co-transfer efficiency, high stability rates, and low fitness costs of mcr-1 and bla<sub>CTX-M</sub> across distinct plasmid types and the mcr-1 selection driven by CEFs support the co-existence of mcr-1 and bla<sub>CTX-M</sub> in E. coli hosts. Our findings support a suggestion that an urgent need for coordinated antibiotic stewardship targeting both drug classes to curb multidrug-resistant bacteria spread.</p>\",\"PeriodicalId\":15936,\"journal\":{\"name\":\"Journal of global antimicrobial resistance\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of global antimicrobial resistance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jgar.2025.08.018\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of global antimicrobial resistance","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jgar.2025.08.018","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Co-existence of mcr-1 and blaCTX-M from porcine-derived Escherichia coli isolated in China and selection of mcr-1 under cephalosporins pressure.
Objectives: The usage of cephalosporins (CEFs) and co-existence of extended-spectrum β-lactamase (ESBL) gene blaCTX-M in the same host may promote the prevalence of colistin (CST) resistance gene mcr-1. This study aims to investigate the underlying mechanisms how the mcr-1 and blaCTX-M demonstrate significant co-occurrence in Escherichia coli (E. coli).
Methods: Conjugation assays were performed on 22 porcine-derived mcr-1-positive and blaCTX-M-positive E. coli (MCRPEC::blaCTX-M+) isolates from China to assess co-transfer potential. Whole genome sequencing characterized the genetic localization and context of mcr-1 and blaCTX-M. Fitness cost and genetic stability were evaluated through growth curve and anti-microbial resistance (AMR) gene stability rates measurement. Additionally, we examined mcr-1 selection during blaCTX-M co-existence under CEFs pressure by monitoring fitness and stability variations in mcr-1.
Results: Successful co-transfer of mcr-1 and blaCTX-M occurred in 36% (8/22) of isolates, demonstrating co-transfer efficiency ranging from 1.3×10-5 to 1.5×10-3. Predominant plasmid combinations facilitating co-transfer were IncI2(mcr-1) + IncI1(blaCTX-M) combination. Notably, we report the first identification of blaCTX-M-positive E. coli (CTX-M-EC) carrying dual mcr-1 copies on plasmids. mcr-1 and blaCTX-M did not exhibit fitness costs in 63% (5/8) of transconjugants, with 88% (7/8) maintaining over 70% stable rate in 10 days. CEFs pressure enhanced both fitness and stability of mcr-1 in blaCTX-M co-harboring transconjugants.
Conclusions: The observed high co-transfer efficiency, high stability rates, and low fitness costs of mcr-1 and blaCTX-M across distinct plasmid types and the mcr-1 selection driven by CEFs support the co-existence of mcr-1 and blaCTX-M in E. coli hosts. Our findings support a suggestion that an urgent need for coordinated antibiotic stewardship targeting both drug classes to curb multidrug-resistant bacteria spread.
期刊介绍:
The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes.
JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR).
Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.