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

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.

Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics

“…Since then, polymyxins have rightfully drawn renewed attention to colistin resistance, and plasmid-mediated colistin resistance by mcr-1 has been reported worldwide in livestock, food and humans (Poirel et al, 2017;Li et al, 2018). The mcr-1 gene confers colistin resistance by encoding a phosphoethanolamine transferase that catalyzes the addition of a phosphoethanolamine moiety to lipid A in the bacterial outer membrane (OM) (Gao et al, 2016;Hinchliffe et al, 2017), which may modify the structure of lipid A and then decrease the growth rate, cell viability, and competitive ability and shape cytoplasmic structures .…”

Applying Nanopore sequencing to a One-Health scenario for colistin resistance transmission among pigs, cows and the farmer

“…Plasmids encountered herein contained similar replicons to the ones described in the literature to be potential carriers of colistin resistance, with IncX4 being the most prevalent [50][51][52][53][54][55][56] . In agreement with other studies 51,[57][58][59] , some of the IncX4 plasmids have lost the transposition element ISApl1 involved in the mobilization of the mcr-1 gene suggesting its stabilization within the plasmid.…”

“…Additionally, the bovine isolate 15B-22 yielded mcr-1 in two different plasmids (IncHI2 and IncX4). Several studies have described coexistence of two mcr-1-harbouring plasmids within a host [52][53][54][55][56] or one copy on a plasmid and the other in the chromosome 53,55,56 .…”

“…As mentioned before, strains carrying mcr-1 in the genome have also been described previously 50,53,55,56 . Interestingly, in our study, mcr-1 was integrated in the genome in two isolates of different origin.…”

Therapeutic Specification of the Last Resort Polymyxins: An Intelligent Approach

“…A study under the SENTRY Antimicrobial Surveillance Program (2006Program ( to 2009 showed that polymyxin B had in vitro characteristics similar to those of colistin against Gramnegative bacteria and the resistance rates were only < 0.1% -1.5% (46). However, over the last few decades, the resistance trends have been increasing in an alarming rate among the most common hospital and/or community pathogens including Klebsiella pneumoniae, Acinetobacter baumannii, multiple Pseudomonas spp., and Escherichia coli worldwide (Table 1) (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57); in some cases, carbapenems-resistant microbial isolates also showed resistance to polymyxins (47,48), making such resistant organism-associated hospital infections difficult-to-treat (Table 1) (47).…”