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Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms
Nature Communications, Volume: 8, Issue: 1
Swansea University Author:
Lydia Powell
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DOI (Published version): 10.1038/s41467-017-02149-0
Abstract
MCR-1 is a lipid A modifying enzyme that confers resistance to the antibiotic colistin. Here, we analyse the impact of MCR-1 expression on E. coli morphology, fitness, competitiveness, immune stimulation and virulence. Increased expression of mcr-1 results in decreased growth rate, cell viability, c...
Published in: | Nature Communications |
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ISSN: | 2041-1723 |
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Springer Science and Business Media LLC
2017
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URI: | https://cronfa.swan.ac.uk/Record/cronfa61622 |
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<?xml version="1.0"?><rfc1807><datestamp>2022-11-09T11:21:46.8326329</datestamp><bib-version>v2</bib-version><id>61622</id><entry>2022-10-20</entry><title>Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms</title><swanseaauthors><author><sid>0e7e702952672bcbfdfd4974199202fb</sid><ORCID>0000-0002-8641-0160</ORCID><firstname>Lydia</firstname><surname>Powell</surname><name>Lydia Powell</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2022-10-20</date><deptcode>BMS</deptcode><abstract>MCR-1 is a lipid A modifying enzyme that confers resistance to the antibiotic colistin. Here, we analyse the impact of MCR-1 expression on E. coli morphology, fitness, competitiveness, immune stimulation and virulence. Increased expression of mcr-1 results in decreased growth rate, cell viability, competitive ability and significant degradation in cell membrane and cytoplasmic structures, compared to expression of catalytically inactive MCR-1 (E246A) or MCR-1 soluble component. Lipopolysaccharide (LPS) extracted from mcr-1 strains induces lower production of IL-6 and TNF, when compared to control LPS. Compared to their parent strains, high-level colistin resistance mutants (HLCRMs) show reduced fitness (relative fitness is 0.41–0.78) and highly attenuated virulence in a Galleria mellonella infection model. Furthermore, HLCRMs are more susceptible to most antibiotics than their respective parent strains. Our results show that the bacterium is challenged to find a delicate equilibrium between expression of MCR-1-mediated colistin resistance and minimalizing toxicity and thus ensuring cell survival.</abstract><type>Journal Article</type><journal>Nature Communications</journal><volume>8</volume><journalNumber>1</journalNumber><paginationStart/><paginationEnd/><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2041-1723</issnElectronic><keywords/><publishedDay>12</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2017</publishedYear><publishedDate>2017-12-12</publishedDate><doi>10.1038/s41467-017-02149-0</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>e thank Dr Jonathan Tyrell (Division of Infection and Immunity, Cardiff University) for useful suggestions on Galleria infection model, Dr M. Toleman (Division of Infection and Immunity, Cardiff University) for his valuable advice on genome sequencing, and Professor W. Jiang (Cardiff China Medical Research Collaborative, Cardiff University) for access to qPCR machine (Applied BiosystemsTM StepOnePlus®, UK). This work was supported by MRC grant DETER-XDR-CHINA (MR/P007295/1). Q.Y. is funded by a CSC Scholarship. D.O.A. benefits a Geneva University Hospitals (HUG) and Swiss National Science Foundation (P300PB_171601) overseas fellowship. 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2022-11-09T11:21:46.8326329 v2 61622 2022-10-20 Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 2022-10-20 BMS MCR-1 is a lipid A modifying enzyme that confers resistance to the antibiotic colistin. Here, we analyse the impact of MCR-1 expression on E. coli morphology, fitness, competitiveness, immune stimulation and virulence. Increased expression of mcr-1 results in decreased growth rate, cell viability, competitive ability and significant degradation in cell membrane and cytoplasmic structures, compared to expression of catalytically inactive MCR-1 (E246A) or MCR-1 soluble component. Lipopolysaccharide (LPS) extracted from mcr-1 strains induces lower production of IL-6 and TNF, when compared to control LPS. Compared to their parent strains, high-level colistin resistance mutants (HLCRMs) show reduced fitness (relative fitness is 0.41–0.78) and highly attenuated virulence in a Galleria mellonella infection model. Furthermore, HLCRMs are more susceptible to most antibiotics than their respective parent strains. Our results show that the bacterium is challenged to find a delicate equilibrium between expression of MCR-1-mediated colistin resistance and minimalizing toxicity and thus ensuring cell survival. Journal Article Nature Communications 8 1 Springer Science and Business Media LLC 2041-1723 12 12 2017 2017-12-12 10.1038/s41467-017-02149-0 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University e thank Dr Jonathan Tyrell (Division of Infection and Immunity, Cardiff University) for useful suggestions on Galleria infection model, Dr M. Toleman (Division of Infection and Immunity, Cardiff University) for his valuable advice on genome sequencing, and Professor W. Jiang (Cardiff China Medical Research Collaborative, Cardiff University) for access to qPCR machine (Applied BiosystemsTM StepOnePlus®, UK). This work was supported by MRC grant DETER-XDR-CHINA (MR/P007295/1). Q.Y. is funded by a CSC Scholarship. D.O.A. benefits a Geneva University Hospitals (HUG) and Swiss National Science Foundation (P300PB_171601) overseas fellowship. P.N. and U.T. are funded by Royal Golden Jubilee-PhD Program from Thailand Research Fund and Rajamangala University of Technology Lanna (PHD/0054/2555). 2022-11-09T11:21:46.8326329 2022-10-20T14:38:06.8071426 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Qiue Yang 1 Mei Li 2 Owen B. Spiller 3 Diego O. Andrey 0000-0003-3247-9274 4 Philip Hinchliffe 5 Hui Li 6 Craig MacLean 0000-0002-7941-813x 7 Pannika Niumsup 8 Lydia Powell 0000-0002-8641-0160 9 Manon Pritchard 10 Andrei Papkou 11 Yingbo Shen 12 Edward Portal 13 Kirsty Sands 14 James Spencer 15 Uttapoln Tansawai 16 David Thomas 17 Shaolin Wang 18 Yang Wang 19 Jianzhong Shen 20 Timothy Walsh 21 61622__25708__8c4d0f2f0422431dad9f82b9e9d4454c.pdf 61622.pdf 2022-11-09T11:20:06.5033144 Output 2249995 application/pdf Version of Record true © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License true eng http://creativecommons.org/licenses/by/4.0/ |
title |
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms |
spellingShingle |
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms Lydia Powell |
title_short |
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms |
title_full |
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms |
title_fullStr |
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms |
title_full_unstemmed |
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms |
title_sort |
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms |
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0e7e702952672bcbfdfd4974199202fb |
author_id_fullname_str_mv |
0e7e702952672bcbfdfd4974199202fb_***_Lydia Powell |
author |
Lydia Powell |
author2 |
Qiue Yang Mei Li Owen B. Spiller Diego O. Andrey Philip Hinchliffe Hui Li Craig MacLean Pannika Niumsup Lydia Powell Manon Pritchard Andrei Papkou Yingbo Shen Edward Portal Kirsty Sands James Spencer Uttapoln Tansawai David Thomas Shaolin Wang Yang Wang Jianzhong Shen Timothy Walsh |
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Nature Communications |
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2017 |
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Swansea University |
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2041-1723 |
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10.1038/s41467-017-02149-0 |
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Springer Science and Business Media LLC |
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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 |
MCR-1 is a lipid A modifying enzyme that confers resistance to the antibiotic colistin. Here, we analyse the impact of MCR-1 expression on E. coli morphology, fitness, competitiveness, immune stimulation and virulence. Increased expression of mcr-1 results in decreased growth rate, cell viability, competitive ability and significant degradation in cell membrane and cytoplasmic structures, compared to expression of catalytically inactive MCR-1 (E246A) or MCR-1 soluble component. Lipopolysaccharide (LPS) extracted from mcr-1 strains induces lower production of IL-6 and TNF, when compared to control LPS. Compared to their parent strains, high-level colistin resistance mutants (HLCRMs) show reduced fitness (relative fitness is 0.41–0.78) and highly attenuated virulence in a Galleria mellonella infection model. Furthermore, HLCRMs are more susceptible to most antibiotics than their respective parent strains. Our results show that the bacterium is challenged to find a delicate equilibrium between expression of MCR-1-mediated colistin resistance and minimalizing toxicity and thus ensuring cell survival. |
published_date |
2017-12-12T04:20:34Z |
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1763754361113018368 |
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11.021648 |