title: Mechanisms of Methicillin Resistance in Staphylococcus aureus.
abstract: Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for β-lactams. This resistance allows cell-wall biosynthesis, the target of β-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile genetic element (SCCmec), the expression of which is controlled through a proteolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; email: sjp97@medschl.cam.ac.uk.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Gavin K
authors.initials: GK
authors.lastname: Paterson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000662:veterinary; D018440:beta-Lactam Resistance
chemical_list: D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; C487789:mecA protein, Staphylococcus aureus
keywords: MRSA; Staphylococcus aureus; antibiotic resistance; methicillin resistance; penicillin-binding protein; β-lactam antibiotics