AUTHOR=Li Baiyuan , Ke Bixia , Zhao Xuanyu , Guo Yunxue , Wang Weiquan , Wang Xiaoxue , Zhu Honghui 

TITLE=Antimicrobial Resistance Profile of mcr-1 Positive Clinical Isolates of Escherichia coli in China From 2013 to 2016

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02514

DOI=10.3389/fmicb.2018.02514

ISSN=1664-302X

ABSTRACT=<p>Multidrug-resistant (MDR) <italic>Escherichia coli</italic> 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 <italic>E. coli.</italic> A plasmid-encoded colistin resistance gene <italic>mcr-1</italic> encoding phosphoethanolamine transferase has been recently described in Enterobacteriaceae. In this study, a total of 123 <italic>E</italic>. <italic>coli</italic> 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 <italic>E. coli</italic> isolates, 9 isolates (7.3%) were resistant to PB and PCR screening showed that seven (5.7%) isolates carried the <italic>mcr-1</italic> 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 <italic>mcr-1</italic> positive isolates. These seven isolates harbored multiple plasmids and are MDR, with six isolates carrying one <italic>mcr-1</italic> positive plasmid and one isolate (14EC033) carrying two <italic>mcr-1</italic> positive plasmids. These eight <italic>mcr-1</italic> positive plasmids belonged to the IncX4, IncI2, and IncP1 types. In addition, the <italic>mcr-1</italic> gene was the solo antibiotic resistance gene identified in the <italic>mcr-1</italic> positive plasmids, while the rest of the antibiotic resistance genes were mostly clustered into one or two plasmids. Interestingly, one <italic>mcr-1</italic> 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 <italic>mcr</italic>-related genes. Multilocus sequence typing (MLST) showed that these <italic>mcr-1</italic> positive <italic>E</italic>. <italic>coli</italic> isolates belonged to five different STs, and three isolates belonged to ST301 which carried multiple virulence factors related to diarrhea. Additionally, the <italic>mcr-1</italic> positive isolates were all susceptible to imipenem (IMP), suggesting that IMP could be used to treat infection caused by <italic>mcr-1</italic> positive <italic>E. coli</italic> isolates. Collectively, this study showed a high occurrence of <italic>mcr-1</italic> positive plasmids in patients with diarrheal diseases of Guangzhou in China and the abolishment of the MCR-1 mediated colistin resistance in one <italic>E. coli</italic> isolate.</p>