PBP4 Mediates β-Lactam Resistance by Altered Function

Penicillin binding protein 4 (PBP4) can provide high-level beta-lactam resistance in Staphylococcus aureus. A series of missense and promoter mutations associated with pbp4 were detected in strains that displayed high-level resistance. We show here that the missense mutations facilitate the beta-lactam resistance mediated by PBP4 and the promoter mutations lead to overexpression of pbp4. Our results also suggest a cooperative interplay among PBPs for beta-lactam resistance.