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

Yang, Qiu, Li, Mei, Spiller, Owen B. ORCID: https://orcid.org/0000-0002-9117-6911, Andrey, Diego O., Hinchliffe, Philip, Li, Hui, MacLean, Craig, Niumsup, Pannika, Powell, Lydia ORCID: https://orcid.org/0000-0002-8641-0160, Pritchard, Manon ORCID: https://orcid.org/0000-0002-5135-4744, Papkou, Andrei, Shen, Yingbo, Portal, Edward, Sands, Kirsty, Spencer, James, Tansawai, Uttapoln, Thomas, David ORCID: https://orcid.org/0000-0001-7319-5820, Wang, Shaolin, Wang, Yang, Shen, Jianzhong and Walsh, Timothy 2017. Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms. Nature Communications 8 , 2054. 10.1038/s41467-017-02149-0

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Dentistry
Medicine
Subjects: Q Science > QR Microbiology
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License.
Publisher: Nature Research
ISSN: 2041-1723
Funders: MRC grant DETER-XDR-CHINA (MR/P007295/1)
Date of First Compliant Deposit: 29 December 2017
Date of Acceptance: 9 November 2017
Last Modified: 11 Oct 2023 21:43
URI: https://orca.cardiff.ac.uk/id/eprint/107807

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