Cold Stress Makes Escherichia coli Susceptible to Glycopeptide Antibiotics by Altering Outer Membrane Integrity

摘要: A poor understanding of the mechanisms by which antibiotics traverse outer membrane remains a considerable obstacle to development novel Gram-negative antibiotics. Herein, we demonstrate that bacterium Escherichia coli becomes susceptible narrow-spectrum antibiotic vancomycin during growth at low temperatures. Heterologous expression an Enterococcus vanHBX resistance cluster in E. confirmed mechanism action was through inhibition peptidoglycan biosynthesis. To understand nature permeability, screened for strains displayed temperature. Surprisingly, observed mutations biosynthesis suppressed activity. Subsequent chemical analysis lipopolysaccharide from vancomycin-sensitive and -resistant suppression correlated with truncations core oligosaccharide lipopolysaccharide. These unexpected observations challenge current provide new insights into susceptibility glycopeptide