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产质粒介导的 AmpC β-内酰胺酶肺炎克雷伯菌引起尿路感染株的遗传多样性及 ESBLs 和 PMQR 基因的共同流行率。

Genetic diversity and co-prevalence of ESBLs and PMQR genes among plasmid-mediated AmpC β-lactamase-producing Klebsiella pneumoniae isolates causing urinary tract infection.

机构信息

Department of Biotechnology, Basic Medical College, Dalian Medical University, Dalian, China.

Department of Nutrition and Food Hygiene, School of Public Health, Dalian Medical University, Dalian, China.

出版信息

J Antibiot (Tokyo). 2021 Jun;74(6):397-406. doi: 10.1038/s41429-021-00413-6. Epub 2021 Mar 4.

Abstract

Klebsiella pneumoniae is an opportunistic pathogen that frequently causes nosocomial urinary tract infection (UTI). The aim of this study was to investigate the prevalence of extended-spectrum β-lactamases (ESBL), plasmid-mediated quinolone resistance (PMQR) genes, in acquired AmpC (ac-AmpC) β‑lactamase‑producing K. pneumoniae isolates from patients with nosocomial UTI and to characterize the transmissibility of plasmids harbouring multiple resistance genes. From January 2017 to June 2018, we collected 46 ac-AmpC-producing K. pneumoniae isolates causing UTI from a tertiary care hospital in China. Antimicrobial susceptibility assays showed that non-susceptibility of all isolates to third-generation cephalosporin and fluoroquinolone was very high (>80%). Diverse types of ESBLs and PMQR genes, including bla (n = 23), bla (n = 1) bla (n = 2) bla (n = 4), bla (n = 24) bla (n = 6) bla (n = 6) bla (n = 1) and bla (n = 26) as well as qnrA (n = 2), qnrB (n = 39) and qnrS (n = 2) genes were identified amongst AmpC-producing K. pneumoniae isolates. The bla qnrB and several ESBLs genes from six strains harbouring multiple AmpC (at least two ampC) were co-transferrable to recipients via conjugation or electroporation, with IncFIA, IncFIB and IncA/C being the dominant replicons. Conserved genetic context associated with the mobilization of bla genes was detected. Forty-six isolates were categorized into 25 enterobacterial repetitive intergenic consensus (ERIC) types, and the 6 isolates harbouring multiple AmpC genes belonged to ST1 lineage. This work reports that the emergence of plasmids co-harbouring multiple resistance determinants and mediating the local prevalence in K. pneumoniae causing UTI in China.

摘要

肺炎克雷伯菌是一种机会致病菌,常引起医院获得性尿路感染(UTI)。本研究旨在调查产获得性 AmpC(ac-AmpC)β-内酰胺酶肺炎克雷伯菌分离株中广泛耐药β-内酰胺酶(ESBL)、质粒介导的喹诺酮耐药(PMQR)基因的流行情况,并对携带多种耐药基因的质粒的传播能力进行表征。2017 年 1 月至 2018 年 6 月,我们从中国一家三级医院收集了 46 株引起 UTI 的 ac-AmpC 产肺炎克雷伯菌分离株。药敏试验结果显示,所有分离株对第三代头孢菌素和氟喹诺酮类药物的非敏感性均很高(>80%)。发现不同类型的 ESBL 和 PMQR 基因,包括 bla(n=23)、bla(n=1)bla(n=2)bla(n=4)、bla(n=24)bla(n=6)bla(n=6)bla(n=1)和 bla(n=26)以及 qnrA(n=2)、qnrB(n=39)和 qnrS(n=2)基因,这些基因在产 AmpC 的肺炎克雷伯菌分离株中均有发现。6 株携带多种 AmpC(至少两种 ampC)的菌株中,bla qnrB 和几种 ESBL 基因可通过接合或电穿孔转移到受体菌中,IncFIA、IncFIB 和 IncA/C 是主要的复制子。检测到与 bla 基因转移相关的保守遗传背景。46 株分离株被分为 25 个肠杆菌重复基因间一致序列(ERIC)型,6 株携带多种 AmpC 基因的分离株属于 ST1 谱系。本研究报告了在中国引起 UTI 的肺炎克雷伯菌中,同时携带多种耐药决定因子的质粒的出现以及介导局部流行情况。

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