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.

Details

Title
Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms
Author
Yang, Qiue 1 ; Li, Mei 1 ; Spiller, Owen B 1 ; Andrey, Diego O 2   VIAFID ORCID Logo  ; Hinchliffe, Philip 3 ; Li, Hui 4 ; MacLean, Craig 5   VIAFID ORCID Logo  ; Niumsup, Pannika 6 ; Powell, Lydia 7 ; Pritchard, Manon 7 ; Papkou, Andrei 5 ; Shen, Yingbo 8 ; Portal, Edward 1 ; Sands, Kirsty 1 ; Spencer, James 3 ; Tansawai, Uttapoln 6 ; Thomas, David 7 ; Wang, Shaolin 8 ; Wang, Yang 8 ; Shen, Jianzhong 8 ; Walsh, Timothy 1 

1  Department of Medical Microbiology and Infectious Disease, Division of Infection and Immunity, Cardiff University, Cardiff, UK 
2  Department of Medical Microbiology and Infectious Disease, Division of Infection and Immunity, Cardiff University, Cardiff, UK; Service of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland 
3  School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK 
4  Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, China 
5  Department of Zoology, University of Oxford, Oxford, UK 
6  Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand 
7  Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK 
8  Beijing Advanced Innovation Centre for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China 
Pages
1-12
Publication year
2017
Publication date
Dec 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-02149-0
ProQuest document ID
1983421004
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.