title: Point mutations in Staphylococcus aureus PBP 2 gene affect penicillin-binding kinetics and are associated with resistance.
abstract: In Staphylococcus aureus, penicillin-binding protein 2 (PBP 2) has been implicated in non-PBP 2a-mediated methicillin resistance. The PBP 2 gene (pbpB) was cloned from an expression library of a methicillin-susceptible strain of S. aureus (209P), and its entire sequence was compared with that of the pbpB gene from strains BB255, BB255R, and CDC6. Point mutations that resulted in amino acid substitutions near the conserved penicillin-binding motifs were detected in BB255R and CDC6, two low-level methicillin-resistant strains. Penicillin binding to PBP 2 in both BB255R and CDC6 is altered, and kinetic analysis indicated that altered binding of PBP 2 by penicillin was due to both lower binding affinity and more rapid release of bound drug. These structural and biochemical changes may contribute to the strains' resistance to beta-lactam antibiotics.
authors.affiliation: Division of Infectious Diseases, San Francisco General Hospital, California 94110.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hackbarth
authors.forename: T
authors.initials: T
authors.lastname: Kocagoz
authors.forename: S
authors.initials: S
authors.lastname: Kocagoz
authors.forename: H F
authors.initials: HF
authors.lastname: Chambers
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015723:Gene Library; D006602:Hexosyltransferases / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D016106:Methicillin Resistance / Q000235:genetics; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism*; D010458:Peptidyl Transferases / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D013211:Staphylococcus aureus / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase