Molecular Epidemiology and Colistin Resistant Mechanism of mcr-Positive and mcr-Negative Clinical Isolated Escherichia coli

Abstract

Transmissible colistin resistance mediated by the mcr gene has been reported worldwide, but clinical isolates of mcr-negative colistin-resistant Escherichia coli are rarely reported. The aim of this study was to evaluate the mechanism of colistin resistance among mcr-positive and mcr-negative E. coli clinical isolates by performing a molecular epidemiological surveillance. For the first time ever, we show nearly the same isolation ratio for mcr-negative and mcr-positive colistin-resistant clinical isolates (47.5 and 52.5%, respectively), with no demonstrable nosocomial transmission. We provide evidence for the prevalence of the mcr-positive IncX4 plasmid and its high potential for horizontal transfer, with no obvious sequence type (ST) preference. In addition, the minimal inhibitory concentrations (MICs) of colistin of the mcr-negative E. coli isolates were obviously higher than those of mcr-positive isolates. Apart from the usually detected genes, i.e., pmrAB, phoPQ, and mgrB, other genes may be associated with the colistin resistance in mcr-negative E. coli. To the best of our knowledge, this is the first paper to report the molecular epidemiological surveillance and the proper mechanism of colistin resistance in mcr-negative E. coli clinical isolates. Together, the results show that colistin resistance was prevalent not only in the mcr-positive clinical E. coli isolates but also in the mcr-negative isolates.

Dissemination and Comparison of Genetic Determinants of mcr-Mediated Colistin Resistance in Enterobacteriaceae via Retailed Raw Meat Products

“…The high diversity of the mcr-1-positive E. coli and K. pneumoniae isolates detected in the present study corresponds to the results for mcr-positive Enterobacteriaceae isolated from different sources (food, animals, and humans) in other studies (Zurfluh et al, 2016;Luo et al, 2017;Roschanski et al, 2017;Zurfluh et al, 2017;El Garch et al, 2018). However, some studies have described an increased prevalence of E. coli with mcr-1 belonging to ST10 obtained from food animals, food, and humans (Zurfluh et al, 2016;El Garch et al, 2018;Shen et al, 2018;Wu et al, 2018).…”

“…The most common type of plasmid was IncX4, which carried the mcr-1 gene in 77% (44/57) of E. coli and K. pneumoniae isolates from turkey meat and liver samples (n = 16) from the Czechia, Germany, Poland, and Brazil. IncX4 plasmids carrying mcr-1 have also been described in E. coli isolated from meat and humans in China Luo et al, 2017;Shen et al, 2018), chicken meat from Brazil (Monte et al, 2017), chicken and turkey meat from the EU (Hasman et al, 2015;Alba et al, 2018), and pigs in Germany (Roschanski et al, 2017). The conjugation assay showed that the majority of IncX4 plasmids carrying mcr-1 were transferable to recipient E. coli cells (14/17).…”

“…E. coli isolates with both chromosomal and plasmid-mediated CT resistance in patients without a history of CT treatment have been detected in China. The fact that more than half of them were farmers suggested the possibility of resistant bacteria transmission to humans in association with agricultural use of antimicrobials (Luo et al, 2017). The level of total sales of antimicrobials to treat farm animals in the Czechia is low compared to in Spain, Italy, Germany, and France (ESVAC, 2018).…”

Collateral sensitivity interactions between antibiotics depend on local abiotic conditions

“…Note our study included only chromosomal mutants derived from a single strain, albeit of an important commensal and opportunistically pathogenic species. Nevertheless, some of the resistance mechanisms we identified are known to be important in natural and clinical populations, such as mutations in genes for efflux pumps ( acr ) 38 , global regulators (marR, phoPQ ) 39–41 and specific antibiotic targets ( ftsI and rpsL ) 42–44 , suggesting our findings are relevant beyond laboratory studies. A key question for future work is whether collateral effects of resistance encoded on plasmids 45,46 , which is common in clinics, show similar sensitivity to abiotic conditions as we saw here.…”

Non-clonal emergence of colistin resistance associated with mutations in the BasRS two-component system in Escherichia coli bloodstream isolates

“…Relatively little is known about colistin resistance mechanisms in E. coli , other than the acquisition of mcr -genes (32). Therefore, we studied a collection of colistin-resistant E. coli strains from bloodstream infections by a combination of whole genome sequencing and matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) analysis of their lipid A, to identify colistin resistance mechanisms in E. coli .…”