Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
The structure was elucidated in this paperNCBI PubMed ID: 26853624Publication DOI: 10.1016/j.chembiol.2015.12.011Journal NLM ID: 101676030Publisher: Cambridge,MA : Cell Press
Correspondence: ebrown
mcmaster.ca
Institutions: Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada, Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8N 3Z5, Canada
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 outer membrane permeability, and provide new chemical insights into the susceptibility of E. coli to glycopeptide antibiotics.
Lipopolysaccharide, Escherichia coli, core oligosaccharide, cluster, Enterococcus, outer membrane, peptidoglycan biosynthesis, glycopeptide antibiotics, mechanism of action, Vancomycin
Structure type: oligomer
Location inside paper: p.273, fig.5B, fraction IIb
Compound class: core oligosaccharide
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130650,IEDB_136906,IEDB_137472,IEDB_140088,IEDB_141794,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_151528,IEDB_190606,IEDB_2189047,IEDB_983931,SB_192,SB_7
Methods: DNA sequencing, SDS-PAGE, ESI-MS, mild acid hydrolysis, genetic methods, GPC, electron microscopy, SEC, immunofluorescence microscopy, screening for vancomycin resistance
Comments, role: Proposed structures of core OS from Y324 mutant strain E. coli grown at 15˚C;
Related record ID(s): 11310, 11711, 11712, 11713
NCBI Taxonomy refs (TaxIDs): 562
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There is only one chemically distinct structure:
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