Methicillin-resistant *Staphylococcus aureus* (MRSA) acquires resistance primarily through the acquisition of the *mecA* gene. This gene encodes for an altered penicillin-binding protein, specifically PBP2a (or PBP2'). PBP2a has a low affinity for beta-lactam antibiotics, including methicillin and other penicillins and cephalosporins, rendering them ineffective. While some *Staphylococcus aureus* strains produce beta-lactamase enzymes (penicillinase) to resist penicillin, this mechanism does not confer resistance to methicillin. Efflux pumps and decreased permeability are less common or primary mechanisms for methicillin resistance in *S. aureus*.
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