PBP2abased

PBP2a-based refers to a mechanism of beta-lactam resistance in Staphylococcus aureus centered on the penicillin-binding protein 2a (PBP2a). PBP2a is a low-affinity transpeptidase that can carry out cell wall synthesis even in the presence of many beta-lactam antibiotics, enabling MRSA strains to survive beta-lactam treatment. The mecA gene encodes PBP2a and is typically carried on the staphylococcal cassette chromosome mec (SCCmec).

Genetic and regulatory features: In most MRSA, mecA is acquired via mobile genetic element SCCmec, and its expression is modulated by regulators such as mecI and mecR1. Some related mecA homologs, such as mecC, also confer PBP2a-like resistance. PBP2a has a transpeptidase domain with an altered active site that binds beta-lactams poorly, allowing continued peptidoglycan crosslinking when other PBPs are inhibited.

Clinical implications and detection: PBP2a-based resistance is the defining feature of MRSA. Rapid PBP2a-based immunoassays and nucleic acid tests detect the protein or mecA/mecC genes to distinguish MRSA from MSSA. Phenotypic methods, such as cefoxitin susceptibility, are used as surrogates for mecA-mediated resistance. PBP2a testing complements routine susceptibility tests and guides antimicrobial therapy.

Therapeutic and research context: beta-lactams with activity against PBP2a, such as ceftaroline, can be effective against MRSA. In addition, understanding PBP2a structure and regulation informs development of new inhibitors. Ongoing surveillance of mec genes and SCCmec types tracks the evolution of PBP2a-based resistance.