TY - JOUR
T1 - Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms
AU - Yang, Qiue
AU - Li, Mei
AU - Spiller, Owen B
AU - Andrey, Diego O
AU - Hinchliffe, Philip
AU - Li, Hui
AU - MacLean, Craig
AU - Niumsup, Pannika
AU - Powell, Lydia
AU - Pritchard, Manon
AU - Papkou, Andrei
AU - Shen, Yingbo
AU - Portal, Edward
AU - Sands, Kirsty
AU - Spencer, James
AU - Tansawai, Uttapoln
AU - Thomas, David
AU - Wang, Shaolin
AU - Wang, Yang
AU - Shen, Jianzhong
AU - Walsh, Timothy
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-017-02149-0
DO - 10.1038/s41467-017-02149-0
M3 - Article (Academic Journal)
C2 - 29233990
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
M1 - 2054
ER -