期刊
Cell Chemical Biology
卷 23, 期 2, 页码 267-277出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2015.12.011
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资金
- Natural Sciences and Engineering Research Council Discovery Grant
- Canadian Institutes of Health Research Foundation Grant
- Canada Research Chairs Program
- Canadian Institutes of Health Operating Grant
- Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program
- Canadian Institutes of Health Research
- Ontario Graduate Scholarships Program
A poor understanding of the mechanisms by which antibiotics traverse the outer membrane remains a considerable obstacle to the development of novel Gram-negative antibiotics. Herein, we demonstrate that the Gram-negative bacterium Escherichia coli becomes susceptible to the narrow-spectrum antibiotic vancomycin during growth at low temperatures. Heterologous expression of an Enterococcus vanHBX vancomycin resistance cluster in E. coli confirmed that the mechanism of action was through inhibition of peptidoglycan biosynthesis. To understand the nature of vancomycin permeability, we screened for strains of E. coli that displayed resistance to vancomycin at low temperature. Surprisingly, we observed that mutations in outer membrane biosynthesis suppressed vancomycin activity. Subsequent chemical analysis of lipopolysaccharide from vancomycin-sensitive and -resistant strains confirmed that suppression was correlated with truncations in the core oligosaccharide of lipopolysaccharide. These unexpected observations challenge the current understanding of outermembrane permeability, and provide new chemical insights into the susceptibility of E. coli to glycopeptide antibiotics.
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