Cross-linking and O-acetylation of peptidoglycan in Staphylococcus aureus (strains H and MR-1) grown in the presence of sub-growth-inhibitory concentrations of beta-lactam antibiotics.
Staphylococcus aureus H was grown for 4 generation times with various sub-growth-inhibitory concentrations of beta-lactam antibiotics specific for particular penicillin-binding proteins (PBPs) - PBP2, clavulanic acid; PBP3, methicillin; PBP4, cefoxitin - and also with the non-specific benzylpenicillin. Isolated cell walls were digested with Chalaropsis muramidase and the resulting peptidoglycan fragments were fractionated by HPLC into disaccharide-peptide monomers and cross-linked dimers, trimers, tetramers and greater oligomers. The pattern of relative fragment concentrations with increasing amounts of drug was roughly the same regardless of the antibiotic used, monomers and dimers increasing while trimers and tetramers changed little and oligomers decreased rapidly. The patterns resembled closely those predicted by the 'random addition' model for multiple cross-link formation and not at all those predicted by the 'monomer addition' model. The O-acetylation of the peptidoglycan remained essentially unaffected under all these conditions. S. aureus MR-1, a constitutive producer of PBP2', gave similar results when treated with methicillin.
Snowden
M A
MA
Glaxo Group Research Ltd. Greenford, Middlesex, UK.
Perkins
H R
HR
D000107:Acetylation; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002440:Cefoxitin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006602:Hexosyltransferases; D007700:Kinetics; D008712:Methicillin / Q000494:pharmacology; D008954:Models, Biological; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D010400:Penicillin G / Q000494:pharmacology; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000378:metabolism*; D010458:Peptidyl Transferases; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002969:Clavulanic Acids; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D019818:Clavulanic Acid; D002440:Cefoxitin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G; D008712:Methicillin