Beta-lactam resistance in Staphylococcus aureus: the adaptive resistance of a plastic genome

Abstract

Staphylococci have two mechanisms for resistance to beta-lactam antibiotics. One is the production of beta-lactamases, enzymes that hydrolytically destroy beta-lactams. The other is the expression of penicillin-binding protein 2a (PBP 2a), which is not susceptible to inhibition by beta-lactam antibiotics. Strains of S. aureus exhibiting either beta-lactamase or PBP 2a-directed resistance (or both) have established a considerable ecological niche among human pathogens. The emergence and subsequent spread of bacterial strains designated as methicillin-resistant S. aureus (MRSA), from the 1960s to the present, has created clinical difficulties for nosocomial treatment on a global scale. The recent variants of MRSA that are resistant to glycopeptide antibiotics (such as vancomycin) have ushered in a new and disconcerting chapter in the evolution of this organism.