Coagulase-negative staphylococci resistant to beta-lactam antibiotics in vivo produce penicillin-binding protein 2a.
Strains of coagulase-negative staphylococci were tested for in vivo resistance in a rabbit model of prophylaxis of endocarditis. Regimens of nafcillin, cefazolin, cefamandole, and vancomycin were compared for efficacy in the prevention of infection caused by two methicillin-resistant strains and a susceptible strain. For the two resistant strains, vancomycin was the most effective drug tested. All regimens were effective against the susceptible strain. The two strains for which prophylaxis with beta-lactam antibiotics failed produced a beta-lactam antibiotic-inducible penicillin-binding protein (PBP) that comigrated in sodium dodecyl sulfate-polyacrylamide gels with the low-affinity PBP 2a that is associated with methicillin resistance in strains of Staphylococcus aureus. Like PBP 2a, this PBP had low binding affinity for beta-lactam antibiotics. Peptide maps after either V8 protease or chymotrypsin digestion of radiolabeled PBP 2a or silver-stained preparations were virtually identical to one another and to maps of PBP 2a from a heterogeneous and a homogeneous strain of S. aureus. Methicillin resistance in coagulase-negative staphylococci and therapeutic failure with beta-lactam antibiotics in vivo is associated with production of PBP 2a, which appears to be highly conserved structurally among different species of staphylococci.
Medical Service, San Francisco General Hospital, California 94110.
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Chambers
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000096:biosynthesis*; D003030:Coagulase / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004697:Endocarditis, Bacterial / Q000382:microbiology / Q000517:prevention & control; D006602:Hexosyltransferases; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis*; D046915:Penicillin-Binding Proteins; D010449:Peptide Mapping; D010458:Peptidyl Transferases; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate; D013050:Spectrometry, Fluorescence; D013210:Staphylococcus / Q000187:drug effects* / Q000201:enzymology; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003030:Coagulase; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; D012967:Sodium Dodecyl Sulfate; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase