Pathogenicity of mcr-1-positive Escherichia coli from human infections
Authors: Cong Shen, Lan-Lan Zhong, Yohei Doi, Nicole Stoesser, Furong Ma, Zihan Zhao, Bin Yan, Guo-Bao Tian
Journal: The Lancet Microbe (2020)

Yan Jiang and colleagues1Jiang Y Zhang Y Lu J et al.Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China: a multicentre case-control and molecular epidemiological study.Lancet Microbe. 2020; 1: e24-e33Summary Full Text Full Text PDF Scopus (8) Google Scholar announced that mcr-1-positive Escherichia coli isolates from human infections were associated with low prevalence, fewer outbreaks, low mortality rates, and a scattered genetic background. Our previous study2Shen C Zhong L-L Yang Y et al.Dynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing-based molecular epidemiological study.Lancet Microbe. 2020; 1: e34-e43Summary Full Text Full Text PDF Scopus (26) Google Scholar found that the genome structure of mcr-1-positive E coli from human infections is different from other sources, which could be associated with the ability of these isolates to cause infection. As Federico Perez and Robert Bonomo3Perez F Bonomo A R Genomic epidemiology of colistin-resistant Escherichia coli in China.Lancet Microbe. 2020; 2: e51-e52Summary Full Text Full Text PDF Scopus (1) Google Scholar commented in regard to our study,2Shen C Zhong L-L Yang Y et al.Dynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing-based molecular epidemiological study.Lancet Microbe. 2020; 1: e34-e43Summary Full Text Full Text PDF Scopus (26) Google Scholar the pathogenicity of mcr-1-positive E coli remains unexplored. To investigate the specific role of mcr-1-positive E coli from human infections, we analysed the functions of 313 gene clusters (including 390 genes) that were significantly present (267 genes) or absent (123 genes) in infection isolates based on pan-genome-wide association analysis (Benjamini-Hochberg adjusted; p<0·0001), and 230 genes that were specifically present in infection isolates, from our previous study (appendix pp 3–4).2Shen C Zhong L-L Yang Y et al.Dynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing-based molecular epidemiological study.Lancet Microbe. 2020; 1: e34-e43Summary Full Text Full Text PDF Scopus (26) Google Scholar The top three enriched COGs (clusters of orthologous groups) among the over-represented genes were carbohydrate transport and metabolism, replication, recombination and repair, and inorganic ion transport and metabolism (appendix p 1). Additionally, our results showed that the top three matched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways among over-represented genes were fructose and mannose metabolism, ABC transporters, and the phosphotransferase system (appendix p 1). Both COG and KEGG results indicate that mcr-1-positive E coli associated with infections could have advantages in metabolism and the transport of carbohydrates. Notably, the merged KEGG pathways showed that the over-represented genes were involved in several carbohydrate-related pathways (appendix p 2). Enhanced fructose and glucose uptake can confer a competitive advantage in glucose utilisation between host cells and mcr-1-positive E coli and promote pathogen virulence.4Troha Katia Janelle S Ayres. Metabolic adaptations to infections at the organismal level.Trends Immunol. 2020; 2: 113-125Summary Full Text Full Text PDF Scopus (12) Google Scholar The mcr-1-positive E coli from human infections have an ability to ingest and use sorbose, which can confer a fitness advantage to virulent E coli clones,5Lehmacher Anselm Bockemuhl Jochen L-Sorbose utilization by virulent Escherichia coli and Shigella: different metabolic adaptation of pathotypes.Int J of Med Microbiol. 2007; 297: 245-254Crossref PubMed Scopus (5) Google Scholar suggesting that these pathogens can better survive, cause infections, and maintain a growth advantage among the competitive microflora.5Lehmacher Anselm Bockemuhl Jochen L-Sorbose utilization by virulent Escherichia coli and Shigella: different metabolic adaptation of pathotypes.Int J of Med Microbiol. 2007; 297: 245-254Crossref PubMed Scopus (5) Google Scholar Our results suggest that the significantly over-represented genes in mcr-1-positive E coli infections encode functions that promote metabolism from carbohydrate ingestion to glycolysis, which might explain their pathogenicity at the metabolic level. We hypothesise that acquisition of accessory genes involved in carbohydrate metabolism allows mcr-1-positive E coli to adopt a metabolic strategy to enhance their ability to infect host cells and outcompete microflora. We declare no competing interests. This work was supported by the National Natural Science Foundation of China (grant numbers: 81722030, 81830103), Guangdong Natural Science Foundation (grant number: 2017A030306012), and project of high-level health teams of Zhuhai 2018 (Innovation Team for Antimicrobial Resistance and Clinical Infection). This online publication has been corrected. The corrected version first appeared at thelancet.com/microbe on December 7, 2020 This online publication has been corrected. The corrected version first appeared at thelancet.com/microbe on December 7, 2020 Download .pdf (1.92 MB) Help with pdf files Supplementary appendix Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China: a multicentre case-control and molecular epidemiological studyThe prevalence of mcr-1-positive E coli infection among patients increased over the study period, although it remained low. Health-care contact was the most probable risk factor. Plasmids are likely to have played a critical role in mcr-1 transmission, rather than clone dissemination and lateral transfer of IS Apl1. Our findings underscore the importance of continued surveillance of E coli strains positive for mcr-1 and potentially other resistance-associated genes, particularly in hospital settings. Full-Text PDF Open AccessDynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing-based molecular epidemiological studyA rapid, ecosystem-wide, decline in mcr-1 was observed after the use of colistin in animal feed was banned, with associated genetic changes in MCRPEC. Withdrawal of antimicrobials from animal feed should be an important One Health measure contributing to the wider control of antimicrobial resistance globally. Full-Text PDF Open AccessGenomic epidemiology of colistin-resistant Escherichia coli in ChinaThe seminal discovery of a mobile genetic determinant of colistin resistance, named mcr-1, among Escherichia coli isolated from food, animal, and human samples in China was first reported in 2015.1 This plasmid-mediated mechanism of resistance was immediately recognised as a threat to human health, given the use of colistin as an antibiotic of last resort to treat infections caused by extensively drug-resistant Gram-negative bacteria. Subsequently, the analysis using whole-genome sequencing (WGS) of 65 isolates from diverse origins discerned that the global population structure of mcr-1-carrying E coli is highly diverse, but dominated by two groups, the largest related to sequence type (ST) 10. Full-Text PDF Open AccessCorrection to Lancet Microbe 2020; 1: e195Shen C, Zhong L-L, Doi Y, et al. Pathogenicity of mcr-1-positive Escherichia coli from human infections. Lancet Microbe 2020; 1: e195—In this Correspondence, the corresponding author should have been Guo-Bao Tian. This correction has been made to the online version as of Dec 7, 2020. Full-Text PDF Open Access