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Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms

Qiue Yang, Mei Li, Owen B. Spiller, Diego O. Andrey Orcid Logo, Philip Hinchliffe, Hui Li, Craig MacLean Orcid Logo, Pannika Niumsup, Lydia Powell Orcid Logo, Manon Pritchard, Andrei Papkou, Yingbo Shen, Edward Portal, Kirsty Sands, James Spencer, Uttapoln Tansawai, David Thomas, Shaolin Wang, Yang Wang, Jianzhong Shen, Timothy Walsh

Nature Communications, Volume: 8, Issue: 1

Swansea University Author: Lydia Powell Orcid Logo

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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...

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Published in: Nature Communications
ISSN: 2041-1723
Published: Springer Science and Business Media LLC 2017
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URI: https://cronfa.swan.ac.uk/Record/cronfa61622
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spelling 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
author_id_str_mv 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
format Journal article
container_title Nature Communications
container_volume 8
container_issue 1
publishDate 2017
institution Swansea University
issn 2041-1723
doi_str_mv 10.1038/s41467-017-02149-0
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
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
active_str 0
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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score 11.021648

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