A ProQ/FinO family protein involved in plasmid copy number control favours fitness of bacteria carrying mcr-1-bearing IncI2 plasmids

Abstract The plasmid-encoded colistin resistance gene mcr-1 challenges the use of polymyxins and poses a threat to public health. Although IncI2-type plasmids are the most common vector for spreading the mcr-1 gene, the mechanisms by which these plasmids adapt to host bacteria and maintain resistanc...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2021-04, Vol.49 (7), p.3981-3996
Main Authors: Yang, Jun, Wang, Hai-Hong, Lu, Yaoyao, Yi, Ling-Xian, Deng, Yinyue, Lv, Luchao, Burrus, Vincent, Liu, Jian-Hua
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Colistin - pharmacology
Drug Resistance, Bacterial - genetics
Escherichia coli - genetics
Escherichia coli Proteins - genetics
Escherichia coli Proteins - physiology
Molecular Biology
Plasmids
RNA-Binding Proteins - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract The plasmid-encoded colistin resistance gene mcr-1 challenges the use of polymyxins and poses a threat to public health. Although IncI2-type plasmids are the most common vector for spreading the mcr-1 gene, the mechanisms by which these plasmids adapt to host bacteria and maintain resistance genes remain unclear. Herein, we investigated the regulatory mechanism for controlling the fitness cost of an IncI2 plasmid carrying mcr-1. A putative ProQ/FinO family protein encoded by the IncI2 plasmid, designated as PcnR (plasmid copy number repressor), balances the mcr-1 expression and bacteria fitness by repressing the plasmid copy number. It binds to the first stem-loop structure of the repR mRNA to repress RepA expression, which differs from any other previously reported plasmid replication control mechanism. Plasmid invasion experiments revealed that pcnR is essential for the persistence of the mcr-1-bearing IncI2 plasmid in the bacterial populations. Additionally, single-copy mcr-1 gene still exerted a fitness cost to host bacteria, and negatively affected the persistence of the IncI2 plasmid in competitive co-cultures. These findings demonstrate that maintaining mcr-1 plasmid at a single copy is essential for its persistence, and explain the significantly reduced prevalence of mcr-1 following the ban of colistin as a growth promoter in China.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkab149