MCR-1: a promising target for structure-based design of inhibitors to tackle polymyxin resistance

Soo Jung Son; Renjie Huang; Christopher J Squire; Ivanhoe K H Leung

doi:10.1016/j.drudis.2018.07.004

MCR-1: a promising target for structure-based design of inhibitors to tackle polymyxin resistance

Drug Discov Today. 2019 Jan;24(1):206-216. doi: 10.1016/j.drudis.2018.07.004. Epub 2018 Jul 20.

Authors

Soo Jung Son¹, Renjie Huang², Christopher J Squire³, Ivanhoe K H Leung⁴

Affiliations

¹ School of Chemical Sciences, The University of Auckland, Victoria Street West, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: aimee.son@auckland.ac.nz.
² School of Chemical Sciences, The University of Auckland, Victoria Street West, Private Bag 92019, Auckland 1142, New Zealand.
³ School of Biological Sciences, The University of Auckland, Victoria Street West, Private Bag 92019, Auckland 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, c/o The University of Auckland, Victoria Street West, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: c.squire@auckland.ac.nz.
⁴ School of Chemical Sciences, The University of Auckland, Victoria Street West, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: i.leung@auckland.ac.nz.

PMID: 30036574
DOI: 10.1016/j.drudis.2018.07.004

Abstract

The spread of a novel mobile colistin resistance gene (mcr1) has jeopardised the use of polymyxins, last-resort antibiotics that are used increasingly to treat infections caused by multidrug-resistant (MDR) Gram-negative pathogens. In early 2017, the WHO reported the global spread of mcr1 within a few years after its initial discovery in China. The protein encoded by mcr1 is a putative 60-kDa phosphoethanolamine (pEtN) transferase, MCR-1, and has been studied extensively since its discovery. Herein, we present a comprehensive review of MCR-1 covering its structure, function, and mechanism, to call for the rational drug design of molecular inhibitors of MCR-1 to use in colistin-based combination therapies.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Anti-Bacterial Agents / pharmacology*
Bacteria / drug effects
Drug Resistance, Bacterial / physiology*
Escherichia coli Proteins / chemistry
Escherichia coli Proteins / physiology*
Microbial Sensitivity Tests
Polymyxins / pharmacology*
Protein Conformation
Transferases / chemistry
Transferases / physiology*

Substances

Anti-Bacterial Agents
Escherichia coli Proteins
MCR-1 protein, E coli
Polymyxins
Transferases