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, 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 and Timothy Walsh ()
Additional contact information
Qiue Yang: Division of Infection and Immunity, Cardiff University
Mei Li: Division of Infection and Immunity, Cardiff University
Owen B. Spiller: Division of Infection and Immunity, Cardiff University
Diego O. Andrey: Division of Infection and Immunity, Cardiff University
Philip Hinchliffe: University of Bristol
Hui Li: Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control
Craig MacLean: University of Oxford
Pannika Niumsup: Faculty of Medical Science, Naresuan University
Lydia Powell: Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park
Manon Pritchard: Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park
Andrei Papkou: University of Oxford
Yingbo Shen: College of Veterinary Medicine, China Agricultural University
Edward Portal: Division of Infection and Immunity, Cardiff University
Kirsty Sands: Division of Infection and Immunity, Cardiff University
James Spencer: University of Bristol
Uttapoln Tansawai: Faculty of Medical Science, Naresuan University
David Thomas: Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park
Shaolin Wang: College of Veterinary Medicine, China Agricultural University
Yang Wang: College of Veterinary Medicine, China Agricultural University
Jianzhong Shen: College of Veterinary Medicine, China Agricultural University
Timothy Walsh: Division of Infection and Immunity, Cardiff University

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-02149-0

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