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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 (2017). 10.1038/s41467-017-02149-0

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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: Dentistry
Advanced Research Computing @ Cardiff (ARCCA)
Subjects: Q Science > QR Microbiology
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: 31 Mar 2020 16:46

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