The rise and spread of mcr plasmid-mediated polymyxin resistance

Abstract

Polymyxins are important lipopeptide antibiotics that serve as the last-line defense against multidrug-resistant (MDR) Gram-negative bacterial infections. Worryingly, the clinical utility of polymyxins is currently facing a serious threat with the global dissemination of mcr, plasmid-mediated polymyxin resistance. The first plasmid-mediated polymyxin resistance gene, termed as mcr-1 was identified in China in November 2015. Following its discovery, isolates carrying mcr, mainly mcr-1 and less commonly mcr-2 to -7, have been reported across Asia, Africa, Europe, North America, South America and Oceania. This review covers the epidemiological, microbiological and genomics aspects of this emerging threat to global human health. The mcr has been identified in various species of Gram-negative bacteria including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella enterica, Cronobacter sakazakii, Kluyvera ascorbata, Shigella sonnei, Citrobacter freundii, Citrobacter braakii, Raoultella ornithinolytica, Proteus mirabilis, Aeromonas, Moraxella and Enterobacter species from animal, meat, food product, environment and human sources. More alarmingly is the detection of mcr in extended-spectrum-β-lactamases- and carbapenemases-producing bacteria. The mcr can be carried by different plasmids, demonstrating the high diversity of mcr plasmid reservoirs. Our review analyses the current knowledge on the emergence of mcr-mediated polymyxin resistance.

Keywords:

• Gram-negative bacteria
• mcr
• polymyxin resistance

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The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

Additional information

Funding

J. L. and T. V. are supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI111965 and AI132154). J. L. is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow. T. V. is an Australian NHMRC Career Development Research Fellow.