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

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Listed:
  • 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
    Geneva University Hospitals and Faculty of Medicine)

  • 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)

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.

Suggested Citation

  • 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 & K, 2017. "Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02149-0
    DOI: 10.1038/s41467-017-02149-0
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    Cited by:

    1. Temitayo Ajayi & Seyedmohammadhossein Hosseinian & Andrew J. Schaefer & Clifton D. Fuller, 2024. "Combination Chemotherapy Optimization with Discrete Dosing," INFORMS Journal on Computing, INFORMS, vol. 36(2), pages 434-455, March.

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