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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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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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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.
College: Faculty of Medicine, Health and Life Sciences
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. 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).
Issue: 1