title: Gradual alterations in cell wall structure and metabolism in vancomycin-resistant mutants of Staphylococcus aureus.
abstract: In five vancomycin-resistant laboratory step mutants selected from the highly and homogeneously methicillin-resistant Staphylococcus aureus strain COL (MIC of methicillin, 800 microg/ml; MIC of vancomycin, 1.5 microg/ml), the gradually increasing levels of resistance to vancomycin were accompanied by parallel decreases in the levels of methicillin resistance and abnormalities in cell wall metabolism. The latter included a gradual reduction in the proportion of highly cross-linked muropeptide species in peptidoglycan, down-regulation of the production of penicillin-binding protein 2A (PBP2A) and PBP4, and hypersensitivity to beta-lactam antibiotics each with a relatively selective affinity for the various staphylococcal PBPs; the PBP2-specific inhibitor ceftizoxime was particularly effective.
authors.affiliation: The Rockefeller University, New York, New York 10021, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sieradzki
authors.forename: A
authors.initials: A
authors.lastname: Tomasz
mesh_terms: D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015296:Ceftizoxime / Q000494:pharmacology; D002473:Cell Wall / Q000378:metabolism* / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D006602:Hexosyltransferases; D007769:Lactams / Q000494:pharmacology; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance / Q000235:genetics; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000378:metabolism; D010458:Peptidyl Transferases; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D014158:Transcription, Genetic; D020713:Vancomycin Resistance / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D007769:Lactams; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D015296:Ceftizoxime; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D008712:Methicillin