PBP2a

PBP2a, or penicillin-binding protein 2a, is a variant of the bacterial penicillin-binding proteins produced by methicillin-resistant Staphylococcus aureus (MRSA). It is encoded by the mecA gene and is carried on the staphylococcal cassette chromosome mec (SCCmec). PBP2a acts as a transpeptidase with a low affinity for beta-lactam antibiotics, allowing MRSA to synthesize peptidoglycan and grow in the presence of methicillin and related drugs.

Most beta-lactams inhibit native PBPs involved in cell-wall cross-linking. PBP2a retains transpeptidase activity despite beta-lactam binding because its active site binds beta-lactams poorly, and it can compensate for inhibited PBPs. Expression of mecA is regulated by regulatory elements such as mecI and mecR1 in many strains, and its upregulation contributes to resistance.

PBP2a production requires mecA expression. The mecA gene is carried on the SCCmec element, a mobile genetic element that varies across MRSA lineages. While most commonly linked to Staphylococcus aureus, mecA can be found in other staphylococcal species, contributing to cross-species beta-lactam resistance via PBP2a.

Clinically, PBP2a-mediated resistance is a defining feature of MRSA. Detection methods include latex agglutination or immunoassays that identify PBP2a, PCR assays for mecA, and phenotypic tests such as cefoxitin disk diffusion, which correlates with PBP2a presence. Ceftaroline and other agents with activity against PBP2a are used to treat MRSA infections, while many beta-lactams are ineffective.