Recent progress on elucidating the molecular mechanism of plasmid-mediated colistin resistance and drug design

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Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing
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Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing

Published on: July 7, 2020

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Jindan Kai1, Sheng Wang2

  • 1Department of Thoracic Surgery, Hubei Cancer Hospital, Wuhan, 430079, China.

International Microbiology : the Official Journal of the Spanish Society for Microbiology
|December 25, 2019
PubMed

Insights

The mobilized colistin resistance gene (mcr-1) confers resistance to last-resort antibiotics. Understanding its enzymatic mechanism is crucial for developing new drugs against pan-drug-resistant bacteria.

Area of Science:

  • Microbiology
  • Drug Resistance
  • Biochemistry

Background:

  • Antibiotic resistance poses a significant global health threat.
  • Polymyxins are critical last-resort antibiotics for treating infections caused by gram-negative bacteria.
  • The emergence of plasmid-mediated transferable polymyxin resistance genes, such as mcr-1, is a growing concern, potentially leading to pan-drug-resistant bacteria.

Purpose of the Study:

  • To review current knowledge on the mobilized colistin resistance gene (mcr-1).
  • To elucidate the detailed enzymatic mechanism of MCR-1.
  • To explore implications for designing novel small molecule inhibitors against polymyxin resistance.

Main Methods:

  • Literature review of studies on mcr-1 and polymyxin resistance.
  • Analysis of the biochemical function of MCR-1 as a phosphoethanolamine transferase.
  • Examination of structure-activity relationships for potential drug design.

Main Results:

  • MCR-1 confers resistance by modifying lipid A through phosphoethanolamine transfer.
  • The enzymatic mechanism involves specific interactions within the bacterial inner membrane.
  • Limited understanding of the precise mechanism hinders the development of effective inhibitors.

Conclusions:

  • MCR-1 represents a critical mechanism for polymyxin resistance in gram-negative bacteria.
  • Elucidating the enzymatic pathway of MCR-1 is essential for combating pan-drug resistance.
  • Targeting MCR-1 with small molecule inhibitors offers a promising strategy for future drug development.
Keywords:
Antibiotic resistanceDrug designMCR-1Polymyxin

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