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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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DOI (Published version): 10.1038/s41396-019-0578-6

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
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URI: https://cronfa.swan.ac.uk/Record/cronfa61614
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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. 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spelling 2022-11-09T12:50:30.0759536 v2 61614 2022-10-20 Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 2022-10-20 BMS 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. Journal Article The ISME Journal 14 3 861 865 Springer Science and Business Media LLC 1751-7362 1751-7370 1 3 2020 2020-03-01 10.1038/s41396-019-0578-6 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 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. 2022-11-09T12:50:30.0759536 2022-10-20T14:31:48.1354673 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Qiu E. Yang 1 Craig MacLean 0000-0002-7941-813x 2 Andrei Papkou 0000-0003-2104-5964 3 Manon Pritchard 4 Lydia Powell 0000-0002-8641-0160 5 David Thomas 6 Diego O. Andrey 0000-0003-3247-9274 7 Mei Li 8 Brad Spiller 9 Wang Yang 0000-0002-5928-9377 10 Timothy R. Walsh 11 61614__25711__f35aa5989eb648a4a0a4c74d08928150.pdf 61614.pdf 2022-11-09T12:49:01.6653038 Output 2221695 application/pdf Version of Record true © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License true eng http://creativecommons.org/licenses/by/4.0/
title Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
spellingShingle Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
Lydia Powell
title_short Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
title_full Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
title_fullStr Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
title_full_unstemmed Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
title_sort Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
author_id_str_mv 0e7e702952672bcbfdfd4974199202fb
author_id_fullname_str_mv 0e7e702952672bcbfdfd4974199202fb_***_Lydia Powell
author Lydia Powell
author2 Qiu E. Yang
Craig MacLean
Andrei Papkou
Manon Pritchard
Lydia Powell
David Thomas
Diego O. Andrey
Mei Li
Brad Spiller
Wang Yang
Timothy R. Walsh
format Journal article
container_title The ISME Journal
container_volume 14
container_issue 3
container_start_page 861
publishDate 2020
institution Swansea University
issn 1751-7362
1751-7370
doi_str_mv 10.1038/s41396-019-0578-6
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description 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.
published_date 2020-03-01T04:20:33Z
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