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 ShenTimothy Walsh

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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.

Original languageEnglish
Article number2054
Number of pages12
JournalNature Communications
Volume8
Early online date12 Dec 2017
DOIs
Publication statusPublished - Dec 2017

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    Yang, Q., Li, M., Spiller, O. B., Andrey, D. O., Hinchliffe, P., Li, H., MacLean, C., Niumsup, P., Powell, L., Pritchard, M., Papkou, A., Shen, Y., Portal, E., Sands, K., Spencer, J., Tansawai, U., Thomas, D., Wang, S., Wang, Y., ... Walsh, T. (2017). Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms. Nature Communications, 8, [2054]. https://doi.org/10.1038/s41467-017-02149-0