Abstract

Multidrug-resistant (MDR) Escherichia coli poses a great challenge for public health in recent decades. Polymyxins have been reconsidered as a valuable therapeutic option for the treatment of infections caused by MDR E. coli. A plasmid-encoded colistin resistance gene mcr-1 encoding phosphoethanolamine transferase has been recently described in Enterobacteriaceae. In this study, a total of 123 E. coli isolates obtained from patients with diarrheal diseases in China were used for the genetic analysis of colistin resistance in clinical isolates. Antimicrobial resistance profile of polymyxin B (PB) and 11 commonly used antimicrobial agents were determined. Among the 123 E. coli isolates, 9 isolates (7.3%) were resistant to PB and PCR screening showed that seven (5.7%) isolates carried the mcr-1 gene. A hybrid sequencing analysis using single-molecule, real-time (SMRT) sequencing and Illumina sequencing was then performed to resolve the genomes of the seven mcr-1 positive isolates. These seven isolates harbored multiple plasmids and are MDR, with six isolates carrying one mcr-1 positive plasmid and one isolate (14EC033) carrying two mcr-1 positive plasmids. These eight mcr-1 positive plasmids belonged to the IncX4, IncI2, and IncP1 types. In addition, the mcr-1 gene was the solo antibiotic resistance gene identified in the mcr-1 positive plasmids, while the rest of the antibiotic resistance genes were mostly clustered into one or two plasmids. Interestingly, one mcr-1 positive isolate (14EC047) was susceptible to PB, and we showed that the activity of MCR-1-mediated colistin resistance was not phenotypically expressed in 14EC047 host strain. Furthermore, three isolates exhibited resistance to PB but did not carry previously reported mcr-related genes. Multilocus sequence typing (MLST) showed that these mcr-1 positive E. coli isolates belonged to five different STs, and three isolates belonged to ST301 which carried multiple virulence factors related to diarrhea. Additionally, the mcr-1 positive isolates were all susceptible to imipenem (IMP), suggesting that IMP could be used to treat infection caused by mcr-1 positive E. coli isolates. Collectively, this study showed a high occurrence of mcr-1 positive plasmids in patients with diarrheal diseases of Guangzhou in China and the abolishment of the MCR-1 mediated colistin resistance in one E. coli isolate.

Highlights

  • Escherichia coli is an important member of the intestinal microbiota of humans and animals (Finegold et al, 1983)

  • The purpose of this study was to determine the prevalence of polymyxin resistance and MDR among the 123 E. coli isolates obtained from patients with diarrheal diseases in China from 2013 to 2016

  • The transmission of colistin resistance gene mcr-1 has been reported to be associated with the food chain (Zurfluh et al, 2017)

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Summary

Introduction

Escherichia coli is an important member of the intestinal microbiota of humans and animals (Finegold et al, 1983). Most E. coli strains are harmless and even benefit the host by preventing colonization of the harmful pathogens (Chang et al, 2004). Pathogenic E. coli has been recognized as an important cause of extraintestinal and intestinal infections in both humans and companion animals (Russo and Johnson, 2003; Wiles et al, 2008). The emergence of E. coli strains showing resistance to broad-spectrum of antimicrobial agents had been reported in the 1980s (Novick, 1981). Emergence of multidrug-resistant (MDR) E. coli has become an urgent global health threat due to the lack of effective antimicrobial agents in recent decades

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