The mcr-9 Gene of Salmonella and Escherichia coli Is Not Associated with Colistin Resistance in the United States

Abstract

Reports of transmissible colistin resistance show the importance of comprehensive colistin resistance surveillance. Recently, a new allele of the mobile colistin resistance (mcr) gene family designated mcr-9, which shows variation in genetic context and colistin susceptibility, was reported. We tested over 100 Salmonella enterica and Escherichia coli isolates with mcr-9 from the National Antimicrobial Resistance Monitoring System (NARMS) in the United States for their susceptibility to colistin and found that every isolate was susceptible, with an MIC of ≤1 μg/ml. Long-read sequencing of 12 isolates revealed mcr-9 on IncHI plasmids that were either independent or integrated into the chromosome. Overall, these results demonstrate that caution is necessary when determining the clinical relevance of new resistance genes.

Genetic Determinants of Resistance to Extended-Spectrum Cephalosporin and Fluoroquinolone in Escherichia coli Isolated from Diseased Pigs in the United States

“…The colistin resistance gene (mcr-9) was recently described for the first time in an S. enterica serovar Typhimurium isolate collected from a human patient in Washington state and was able to confer colistin resistance to E. coli isolates cloned with this gene (89). Tyson et al further evaluated the presence of this gene in Salmonella and E. coli collected from animal meat in the United States and found that this gene was present on large IncHI2 plasmids similar to those found here or integrated into bacterial chromosomes (90). Tyson et al also found that mcr-9-carrying bacterial isolates were all susceptible to colistin (90); hence, the clinical relevance of this gene on human health is still debatable.…”

Genomic Insights of Multidrug-Resistant Escherichia coli From Wastewater Sources and Their Association With Clinical Pathogens in South Africa

“…the mcr-9 gene may not be associated with colistin resistance (23). In this study, the mcr-9 gene was found adjacent to an unknown function cupin fold metalloprotein gene (WbuC) in genetic context mcr-9:WbuC:IS6 (IS26).…”

Circulation of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli of Pandemic Sequence Types 131, 648, and 410 Among Hospitalized Patients, Caregivers, and the Community in Rwanda

“…This phenomenon was first reported in 2019 (Carroll et al, 2019;Kieffer et al, 2019). Due to the structural heterogeneity compared to other mcr genes (65% amino acid identity with the most closely related mcr-3 gene) and the weak inactivation of colistin, the clinical importance of mcr-9 is unknown (Tyson et al, 2020).…”

“…Two strains (1.7%; 2/120) belonging to ST181 and ST540 were carriers of mcr-9 but showed phenotypic susceptibility to colistin, which is a last-resort antibiotic (MIC of both strains: 0.5 µg/mL). Interestingly, previous studies suggest that this latest member of the mcr gene family does not always confer phenotypic resistance to colistin in clinical isolates, although overexpression in E. coli TOP10 cells leads to increased MICs (Carroll et al, 2019;Kieffer et al, 2019;Tyson et al, 2020).…”