MRSA is resistant to the beta-lactam antibiotics. The term methicillin-resistant is historically used to describe resistance to any of this antimicrobial class even though methicillin is no longer the drug of choice. The acronym MRSA persists and is used interchangeably with oxacillin-resistant Staphylococcus aureus (ORSA). Oxacillin/methicillin resistance implies resistance to all penicillins, cephalosporins, monobactams, carbapenems, and beta-lactam/beta-lactamase inhibitor combinations.
S. aureus intrinsically produces beta-lactamase enzymes that break down beta-lactam antibiotics (e.g., penicillin); these are designated PBP 1 – 4. The beta-lactam resistance of MRSA is determined by the production of a penicillin-binding protein called PBP 2' (PBP 2a), which has a reduced binding affinity for beta-lactam antibiotics. This allows MRSA strains to continue cell wall synthesis due to the uninhibited activity of PBP2' even in the presence of otherwise inhibitory concentrations of beta-lactam antibiotics.
PBP2' is encoded by a mecA gene located on the MRSA chromosome and is widely distributed among S. aureus as well as coagulase-negative staphylococci. The mecA gene is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec – SCCmec that is integrated into the bacterial chromosome.
The mecA gene is believed to have originated in some coagulase-negative staphylococcal strains and was then transferred into S. aureus, giving rise to MRSA. It is likely that SCCmec serves as the carrier of the mecA gene moving across staphylococcal species as these mecA genes have never been found without the presence of an SCCmec-like structure. Phylogenetic analyses of international collections of MRSA and methicillin-susceptible S. aureus isolates have revealed that methicillin resistance has arisen in five distinct lineages designated SCCmec I – V, which differ in both size and genetic composition. In recent years, the gene has continued to evolve so that many MRSA strains are currently resistant to several different antibiotics.
