Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms
Nature Publishing Group, 2017
Online
academicJournal
Zugriff:
Background. Mobile colistin resistance, MCR-1, is a lipid A modifying mechanism. Despite is global dissemination, the impact of mcr-1 expression bacterial fitness and pathogenicity is poorly understood. Accordingly, we analysed the impact of MCR-1 on bacterial morphological changes, fitness, competitiveness, immune stimulation and pathogenicity. Results. Increased expression of mcr-1 resulted in decreased in vitro growth rate, cell viability, competitive ability and significant degradation in cell membrane structure and cytoplasm compared to mcr-1 (E246A) and mcr-1 (soluble component). Stimulation of IL-6 and TNF production by lipopolysaccharide (LPS) extracted from mcr-1 strains were diminished, when compared to control LPS. Furthermore, overexpression (11-fold) of mcr-1 in wild-type E. coli s impacted the bacteria’s killing ability in a Galleria mellonella model. Compared to their parent strains, high-level colistin resistance mutants (HLCRMs) have reduced fitness (relative fitness is 0.41-0.78) with a striking reduction in pathogenicity and killing ability in a G. mellonella model. Sequencing analysis of HLCRMs and their parent strains, showed that only two mutants (PN25 and PN42) had mutations in previously recognised loci (PmrA (R81S) and PmrB (V161M)) associated with colistin resistance. Antibiotic MICs from mutants showed they were more susceptible to most antibiotics than their respective parent strains. Significance of Findings. Our data, shows that the bacterium is challenged to find a delicate equilibrium between expression of MCR-1 mediated colistin resistance and minimalizing toxicity or cell survival/competitiveness.
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Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms
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Autor/in / Beteiligte Person: | Yang, Q ; Mei, L ; Spiller, O ; Andrey, D ; Hincliffe, P ; Li, H ; Maclean, R ; Niumsup, P ; Powell, L ; Pritchard, M ; Papkou, A ; Shen, Y ; Portal, E ; Sands, K ; Spencer, J ; Tansawai, U ; Thomas, D ; Wang, S ; Wang, Y ; Shen, J ; Walsh, T |
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Veröffentlichung: | Nature Publishing Group, 2017 |
Medientyp: | academicJournal |
DOI: | 10.1038/s41467-017-02149-0 |
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