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Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
The ISME Journal, Volume: 14, Issue: 3, Pages: 861 - 865
Swansea University Author:
Lydia Powell
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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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ISSN: | 1751-7362 1751-7370 |
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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. 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.</abstract><type>Journal Article</type><journal>The ISME Journal</journal><volume>14</volume><journalNumber>3</journalNumber><paginationStart>861</paginationStart><paginationEnd>865</paginationEnd><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>1751-7362</issnPrint><issnElectronic>1751-7370</issnElectronic><keywords/><publishedDay>1</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2020</publishedYear><publishedDate>2020-03-01</publishedDate><doi>10.1038/s41396-019-0578-6</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>This work was supported by MRC grant DETER-XDR-CHINA-HUB (MR/S013768/1). 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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 |
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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 |
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The ISME Journal |
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14 |
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861 |
publishDate |
2020 |
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Swansea University |
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1751-7362 1751-7370 |
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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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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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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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1763754360128405504 |
score |
11.021648 |