A role in vivo for penicillin-binding protein-4 of Staphylococcus aureus.
The degree of cross-linking of the peptidoglycan of Staphylococcus aureus H and mutants lacking penicillin-binding proteins 1 and 4 was studied. No major changes were observed in organisms lacking protein 1 whereas loss of protein 4 was accompanied by a marked reduction in the degree of cross-linking and the absence of a membrane-bound 'model' transpeptidase activity. A similar effect was achieved when cultures of the staphylococci were treated with the beta-lactam antibiotic cefoxitin. At low concentrations (0.05 microgram ml-1) cefoxitin shows highest affinity for protein 4 to which it appears to bind irreversibly. Treatment of the mutant lacking protein 4 with this concentration of the antibiotic did not affect the degree of cross-linkage. The possibility that the decrease in cross-linkage was a consequence of DD-carboxypeptidase activity on peptidoglycan precursors was investigated. Although both S. aureus H and the mutants possessed such activity it was insensitive to benzylpenicillin and cefoxitin and the role of this enzyme(s) in peptidoglycan biosynthesis remains unknown. We conclude that in vivo protein 4 acts as a transpeptidase involved in the secondary cross-linking of peptidoglycan and this activity is necessary to achieve the high degree of cross-linkage observed in the peptidoglycan of staphylococci.
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002440:Cefoxitin / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology; D010458:Peptidyl Transferases; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D002440:Cefoxitin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase