A role in vivo for penicillin-binding protein-4 of Staphylococcus aureus

Eur J Biochem. 1981 Oct;119(2):389-93. doi: 10.1111/j.1432-1033.1981.tb05620.x.

Abstract

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.

MeSH terms

  • Bacterial Proteins*
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cefoxitin / pharmacology
  • Cephalosporins / pharmacology
  • Hexosyltransferases*
  • Muramoylpentapeptide Carboxypeptidase / metabolism
  • Penicillin-Binding Proteins
  • Penicillins / pharmacology
  • Peptidyl Transferases*
  • Species Specificity
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / metabolism*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Cephalosporins
  • Penicillin-Binding Proteins
  • Penicillins
  • Cefoxitin
  • Peptidyl Transferases
  • Hexosyltransferases
  • Muramoylpentapeptide Carboxypeptidase