An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci

Research output: Contribution to journalArticlepeer-review

244 Citations (Scopus)

Abstract

The blanket resistance of methicillin-resistant Staphylococcus aureus to all β-lactam antibiotics - which had such a devastating impact on chemotherapy of staphylococcal infections - is related to the properties of the key component of this resistance mechanism: the "acquired" penicillin-binding protein (PBP)-2A, which has unusual low affinity for all β-lactam antibiotics. Until now, the accepted model of resistance implied that in the presence of β-lactam antibiotics in the surrounding medium, PBP2A must take over the biosynthesis of staphylococcal cell wall from the four native staphylococcal PBPs because the latter become rapidly acylated and inactivated at even low concentrations of the antibiotic. However, recent observations indicate that this model requires revision. Inactivation of the transglycosylase domain, but not the transpeptidase domain, of PBP2 of S. aureus prevents expression of β-lactam resistance, despite the presence of the low-affinity PBP2A. The observations suggest that cell-wall synthesis in the presence of β-lactam antibiotics requires the cooperative functioning of the transglycosylase domain of the native staphylococcal PBP2 and the transpeptidase domain of the PBP2A, a protein imported by S. aureus from an extra species source.

Original languageEnglish
Pages (from-to)10886-10891
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number19
DOIs
Publication statusPublished - 11 Sep 2001

Fingerprint Dive into the research topics of 'An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci'. Together they form a unique fingerprint.

Cite this