mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae . mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli . Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE ( Enterococcus faecium , Staphylococcus aureus , K. pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli , K. pneumoniae , A. baumannii , and P. aeruginosa . Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli , K. pneumoniae , and A. baumannii but only moderately reduced susceptibility in P. aeruginosa . Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii . Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmid-mediated phosphoethanolamine transferases in general.

(2018). Monitoring Colistin Resistance in Food Animals, An Urgent Threat. Expert Review of Anti-infective Therapy: Vol. 16, No. 6, pp. 443-446.

Plasmid-mediated colistin resistance genemcr-1generally confers low-level resistance. The purpose of this study was to investigate the impact ofmcr-1on the development of high-level colistin resistance (HLCR) inKlebsiella pneumoniaeandEscherichia coli. In this study,mcr-1-negativeK. pneumoniaeandE. colistrains and their correspondingmcr-1-positive transformants were used to generate HLCR mutantsviamultiple passages in the presence of increasing concentrations of colistin. We found that forK. pneumoniae, HLCR mutants with minimum inhibitory concentrations (MICs) of colistin from 64 to 1,024 mg/L were generated. Colistin MICs increased 256- to 4,096-fold formcr-1-negativeK. pneumoniaestrains but only 16- to 256-fold for themcr-1-harboring transformants. ForE. coli, colistin MICs increased 4- to 64-folds, but only 2- to 16-fold for theirmcr-1-harboring transformants. Notably,mcr-1improved the survival rates of bothE. coliandK. pneumoniaestrains when challenged with relatively high concentrations of colistin. In HLCRK. pneumoniaemutants, amino acid alterations predominately occurred incrrB, followed byphoQ,crrA,pmrB,mgrB, andphoP, while inE. colimutants, genetic alterations were mostly occurred inpmrBandphoQ. Additionally, growth rate analyses showed that the coexistence ofmcr-1and chromosomal mutations imposed a fitness burden on HLCR mutants ofK. pneumoniae. In conclusion, HLCR was more likely to occur inK. pneumoniaestrains thanE. colistrains when exposed to colistin. Themcr-1gene could improve the survival rates of strains of both bacterial species but could not facilitate the evolution of high-level colistin resistance.