title: Increased glycan chain length distribution and decreased susceptibility to moenomycin in a vancomycin-resistant Staphylococcus aureus mutant.
abstract: A vancomycin-resistant Staphylococcus aureus mutant, COL-VR1 (MIC, 16 microg/ml), was isolated from methicillin-resistant S. aureus COL by exposure to vancomycin. COL-VR1 also showed decreased susceptibility to teicoplanin (8-fold), methicillin (2-fold), macarbomycin (8-fold), and moenomycin (16-fold). Macarbomycin and moenomycin are thought to directly inhibit transglycosylase activity. Characterization of the mutant revealed a thickened cell wall and suppression of penicillin-induced lysis, although the amounts of the five penicillin-binding proteins (PBPs 1, 2, 3, 4, and 2') and the profiles of peptidoglycan hydrolases were not altered. Analysis of muropeptide profile and glycan chain length distribution by reversed-phase high-pressure liquid chromatography revealed slightly decreased peptide cross-linking and an increased average glycan chain length compared to those of the parent. These results together suggest that a transglycosylase activity was enhanced in the mutant. This may represent a novel mechanism of glycopeptide resistance in S. aureus.
authors.affiliation: Department of Microbiology, Hiroshima University Faculty of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima City, Hiroshima 734-8553, Japan. hkomatsu@ipc.hiroshima-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komatsuzawa
authors.forename: Kouji
authors.initials: K
authors.lastname: Ohta
authors.forename: Sakuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ehlert
authors.forename: Harald
authors.initials: H
authors.lastname: Labischinski
authors.forename: Junko
authors.initials: J
authors.lastname: Kajimura
authors.forename: Tamaki
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Sugai
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015169:Colony Count, Microbial; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D009154:Mutation; D009844:Oligosaccharides / Q000494:pharmacology*; D010457:Peptidoglycan / Q000032:analysis; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D020713:Vancomycin Resistance / Q000502:physiology*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D009844:Oligosaccharides; D010457:Peptidoglycan; D011134:Polysaccharides; C419802:moenomycin