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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.

, Andrey, Diego O., Hinchliffe, Philip, Li, Hui, MacLean, Craig, Niumsup, Pannika, Powell, Lydia

, Pritchard, Manon

, Papkou, Andrei, Shen, Yingbo, Portal, Edward, Sands, Kirsty, Spencer, James, Tansawai, Uttapoln, Thomas, David

, 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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Official URL: http://dx.doi.org/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, 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:	30 May 2024 12:21
URI:	https://orca.cardiff.ac.uk/id/eprint/107807