Molecular antibiotic resistance mechanisms and co-transmission of the mcr-9 and metallo-beta-lactamase genes in carbapenem-resistant Enterobacter cloacae complex

作者全名："Jiang, Shan; Wang, Xiaoyu; Yu, Haidong; Zhang, Jisheng; Wang, Jianmin; Li, Jie; Li, Xinhui; Hu, Kewang; Gong, Xue; Gou, Xuemei; Yang, Yang; Li, Chunjiang; Zhang, Xiaoli"

作者地址："[Jiang, Shan; Wang, Xiaoyu; Zhang, Jisheng; Wang, Jianmin; Li, Jie; Li, Xinhui; Hu, Kewang; Gong, Xue; Gou, Xuemei; Yang, Yang; Zhang, Xiaoli] Chongqing Med Univ, Dept Microbiol, Yongchuan Hosp, Chongqing, Peoples R China; [Jiang, Shan] Jiamusi Univ, Dept Pathogen Biol, Sch Basic Med, Jiamusi, Peoples R China; [Wang, Xiaoyu] Jiamusi Univ, Dept Microbiol, Affiliated Hosp 1, Jiamusi, Peoples R China; [Yu, Haidong] Shenzhen Univ, Dept Microbiol, Gen Hosp, Shenzhen, Peoples R China; [Hu, Kewang] Zhejiang Univ, Affiliated Hangzhou Xixi Hosp, Dept Microbiol, Sch Med, Hangzhou, Peoples R China; [Li, Chunjiang] Mudanjiang Normal Univ, Dept Life Sci & Technol, Mudanjiang, Peoples R China"

通信作者："Zhang, XL (通讯作者)，Chongqing Med Univ, Dept Microbiol, Yongchuan Hosp, Chongqing, Peoples R China.; Li, CJ (通讯作者)，Mudanjiang Normal Univ, Dept Life Sci & Technol, Mudanjiang, Peoples R China."

来源：FRONTIERS IN MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000885049600001

JCR分区：Q2

影响因子：5.2

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：carbapenem-resistant Enterobacter cloacae complex; mcr-9; metatto-beta-lactamase genes; whole-genome sequencing; IncHI2/2A; colistin

摘要："Carbapenem-resistant Enterobacter cloacae complex (CRECC) has increasingly emerged as a major cause of healthcare-associated infections, with colistin being one of the last-resort antibiotics of treatment. Mobile colistin resistance (mcr)-9 is a member of a growing family of mcr genes and has been reported to be an inducible gene encoding an acquired phosphoethanolamine transferase. Here, we collected 24 ECC strains from Chongqing, China from 2018 to 2021. Subsequently, antibiotic resistance genes and the transmission dynamics of the strains were determined by PCR, whole-genome sequencing, and bioinformatic analysis. The mcr-9 was identified in IncHI2/2A or IncHI2/2A + IncN plasmids from six CRECC strains and was co-located with bla(NDM-1) or bla(IMP-4) in 2/6 plasmids. The genetic environment of mcr-9.1 was composed of IS903B-mcr-9.1-wbuC-IS26 in the five mcr-9.1-harboring-plasmid, but IS1B was located downstream of mcr-9.2 in the pECL414-1 sequence. We also found that the pNDM-068001 plasmid carrying mcr-9.1 could be a hybrid plasmid, formed by a Tn6360-like blaNDM-1 region inserted into an mcr-9.1-positive IncHI2/2A plasmid. A conjugation assay showed that plasmids mediated the co-dissemination of mcr-9 and metallo-beta-lactamase (MBL) genes. In addition, we performed induction assays with sub-inhibitory concentrations of colistin and found an increase in the relative expression levels of the mcr-9.2, qseC, and qseB genes, as well as an increase in the minimum inhibitory concentration values of colistin in the CRECC414 strain. These findings provide a basis for studying the regulatory mechanisms of mcr-9 expression and highlight the importance of effective monitoring to assess the prevalence of MBL and mcr-9 co-existing plasmids."

基金机构："General projects of Chongqing Natural Science Foundation; Yongchuan Natural Science Foundation; Talent introduction project of Yongchuan Hospital of Chongqing Medical University; Program for Youth Innovation in Future Medicine, Chongqing Medical University; [cstc2020jcyj-msxm0067]; [2021yc-jckx20053]; [YJYJ202004]; [YJYJ202005]; [W0113]"

基金资助正文："Funding This work was supported by General projects of Chongqing Natural Science Foundation (cstc2020jcyj-msxm0067), Yongchuan Natural Science Foundation (2021yc-jckx20053), Talent introduction project of Yongchuan Hospital of Chongqing Medical University (YJYJ202004 and YJYJ202005), and Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0113)."