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Dissemination and Mechanism for the MCR-1 Colistin Resistance

Rongsui Gao1, Yongfei Hu2, Zhencui Li1

  • 1Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Plos Pathogens
|November 29, 2016
PubMed

Insights

The MCR-1 gene confers colistin resistance by requiring specific protein regions. This discovery provides crucial insights into the mechanism of resistance against last-resort antibiotics.

Area of Science:

  • Microbiology
  • Genomics
  • Molecular Biology

Background:

  • Polymyxins are critical last-resort antibiotics against multidrug-resistant Gram-negative bacteria.
  • The emergence of plasmid-borne colistin resistance gene (mcr-1) poses a significant threat to public health.
  • Mechanisms underlying MCR-1 mediated colistin resistance remain poorly understood.

Purpose of the Study:

  • To investigate the diversity of mcr-1 gene transfer via plasmids.
  • To elucidate the mechanistic basis of MCR-1 mediated colistin resistance.
  • To explore the evolutionary origins of MCR-1.

Main Methods:

  • Comparative genomics of mcr-1 harbouring plasmids from human gut microbiota.
  • Genetic dissection to identify essential regions for MCR-1 function.
  • Biochemical preparation and verification of the soluble MCR-1 protein.
  • Phylogenetic analyses of MCR-1 and related proteins.

Main Results:

  • Identified diversity in plasmid-mediated transfer of the mcr-1 gene.
  • Determined that both trans-membrane region and substrate-binding motif are crucial for MCR-1 resistance.
  • Successfully prepared and verified the soluble MCR-1 protein.
  • Revealed high homology of MCR-1 to Paenibacillus PEA lipid A transferase and potential parallel evolution with Neisseria LptA.

Conclusions:

  • Provides the first mechanistic insights into MCR-1 mediated colistin resistance.
  • Highlights the importance of specific protein domains for MCR-1 function.
  • Suggests potential convergent evolution pathways for colistin resistance genes.

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