Multidrug-resistant Shigella sonnei carrying the plasmid-mediated mcr-1 gene in China

Int J Antimicrob Agents. 2018 Jul;52(1):14-21. doi: 10.1016/j.ijantimicag.2018.02.019. Epub 2018 Feb 28.

Abstract

Since the plasmid-mediated polymyxin resistance gene mcr-1 was first reported in Escherichia coli and Klebsiella pneumoniae in China, only one mcr-1-positive isolate of Shigella sonnei, containing inactivated mcr-1, has been reported worldwide. In this study, 1650 historical S. sonnei strains isolated from 2003-2015 in China were screened for the mcr-1 gene. Antimicrobial susceptibilities and resistance genes of mcr-1-positive isolates were determined, and the transferability of polymyxin resistance by plasmid conjugation was investigated. Pulsed-field gel electrophoresis (PFGE), plasmid profiles and Southern blotting were used to analyse genetic relationships and plasmid characteristics, and mcr-1-positive plasmids were sequenced. Six mcr-1-positive S. sonnei isolates from Shanghai (2010-2012) with polymyxin B resistance (MICs 4-8 μg/mL) were identified. Four of these exhibited multidrug resistance, including resistance to azithromycin and third-generation cephalosporins, and co-harboured blaCTX-M-14, mph(A) and blaTEM on different plasmids. mcr-1-positive plasmids shared highly similar IncI2 backbones that resembled reference plasmids, although some differences were observed, including various and abundant insertion sequences/patterns (IS1294, IS1 and ISApl1) and a diverse recombination shufflon region. mcr-1 in S. sonnei may date back to mid-2006. Here we report for the first time the presence of active mcr-1 in multidrug-resistant S. sonnei in China, which has existed since at least 2010. This study highlights the diverse mobile genetic elements on mcr-1-harboring plasmids, potentially resulting in high rates of mcr-1 horizontal transfer among Enterobacteriaceae. These findings emphasise the importance of continuous national and international surveillance of mcr-1-positive Shigella and changes in antibiotic resistance patterns.

Keywords: MDR; Multidrug-resistant; Shigella sonnei; mcr-1.

MeSH terms

  • Adult
  • Bacterial Proteins / genetics*
  • Blotting, Southern
  • China
  • Conjugation, Genetic
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Dysentery, Bacillary / microbiology
  • Electrophoresis, Gel, Pulsed-Field
  • Humans
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • Polymyxin B / pharmacology
  • Shigella sonnei / drug effects*
  • Shigella sonnei / genetics*
  • Shigella sonnei / isolation & purification

Substances

  • Bacterial Proteins
  • Polymyxin B