title: Peptidoglycan composition of a highly methicillin-resistant Staphylococcus aureus strain. The role of penicillin binding protein 2A.
abstract: All clinical isolates of methicillin-resistant Staphylococcus aureus contain an extra penicillin binding protein (PBP) 2A in addition to four PBPs present in all staphylococcal strains. This extra PBP is thought to be a transpeptidase essential for the continued cell wall synthesis and growth in the presence of beta-lactam antibiotics. As an approach of testing this hypothesis we compared the muropeptide composition of cell walls of a highly methicillin-resistant S. aureus strain containing PBP2A and its isogenic Tn551 derivative with reduced methicillin resistance, which contained no PBP2A because of the insertional inactivation of the PBP2A gene. Purified cell walls were hydrolyzed into muropeptides which were subsequently resolved by reversed-phase high-performance liquid chromatography and identified by chemical and mass spectrometric analysis. The peptidoglycan composition of the two strains were identical. Both peptidoglycans were highly cross-linked mainly through pentaglycine cross-bridges, although other, chemically distinct peptide cross-bridges were also present including mono-, tri-, and tetraglycine; alanine; and alanyl-tetraglycine. Our experiments provided no experimental data for a unique transpeptidase activity associated with PBP2A.
authors.affiliation: Laboratory of Microbiology, Rockefeller University, New York, New York 10021.
authors.forename: B L
authors.initials: BL
authors.lastname: de Jonge
authors.forename: Y S
authors.initials: YS
authors.lastname: Chang
authors.forename: D
authors.initials: D
authors.lastname: Gage
authors.forename: A
authors.initials: A
authors.lastname: Tomasz
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002473:Cell Wall / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004352:Drug Resistance, Microbial; D006602:Hexosyltransferases / Q000378:metabolism*; D008712:Methicillin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000378:metabolism*; D010458:Peptidyl Transferases / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D008712:Methicillin