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PLoS Pathog. 2016 Nov 28;12(11):e1005957. doi: 10.1371/journal.ppat.1005957. eCollection 2016 Nov.

Dissemination and Mechanism for the MCR-1 Colistin Resistance.

Author information

1
Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
2
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
3
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China.
4
Department of Biochemistry, University of Illinois, Urbana, Illinois, United States of America.
5
Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Abstract

Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1). However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA) potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance.

PMID:
27893854
PMCID:
PMC5125707
DOI:
10.1371/journal.ppat.1005957
[Indexed for MEDLINE]
Free PMC Article

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