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Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones

Qiu E. Yang, Craig MacLean Orcid Logo, Andrei Papkou Orcid Logo, Manon Pritchard, Lydia Powell Orcid Logo, David Thomas, Diego O. Andrey Orcid Logo, Mei Li, Brad Spiller, Wang Yang Orcid Logo, Timothy R. Walsh

The ISME Journal, Volume: 14, Issue: 3, Pages: 861 - 865

Swansea University Author: Lydia Powell Orcid Logo

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Abstract

The emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition ass...

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Published in: The ISME Journal
ISSN: 1751-7362 1751-7370
Published: Springer Science and Business Media LLC 2020
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa61614
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Abstract: The emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition assays. mcr-3 expression confers a lower fitness cost than mcr-1, as determined by competitive ability and cell viability. Consistent with these findings, plasmids carrying mcr-3 have higher stability than mcr-1 plasmids across a range of Escherichia coli strains. Crucially, mcr-3 plasmids can stably persist, even in the absence of colistin. Recent compensatory evolution has helped to offset the cost of mcr-3 expression, as demonstrated by the high fitness of mcr-3.5 as opposed to mcr-3.1. Reconstructing all of the possible evolutionary trajectories from mcr-3.1 to mcr-3.5 reveals a complex fitness landscape shaped by negative epistasis between compensatory and neutral mutations. Our findings highlight the importance of fitness costs and compensatory evolution in driving the dynamics and stability of mobile colistin resistance in bacterial populations, and they highlight the need to understand how processes (other than colistin use) impact mcr dynamics.
College: Faculty of Medicine, Health and Life Sciences
Funders: This work was supported by MRC grant DETER-XDR-CHINA-HUB (MR/S013768/1). DOA benefits a Geneva University Hospitals (HUG) and Swiss National Science Foundation (P300PB_171601) overseas fellowship. CM is supported by Wellcome Trust Grant 106918/Z/15/Z.
Issue: 3
Start Page: 861
End Page: 865