Beta-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is due to production of PBP2a, encoded by the mecA gene. PBP2a confers resistance primarily by which property?

• A Very low affinity for beta-lactam antibiotics, allowing continued transpeptidation ✓
• B Enzymatic hydrolysis of the beta-lactam ring via serine esterase activity
• C Efflux pump upregulation that exports beta-lactams before PBP binding
• D Altered porin channels preventing drug entry into the cell

Explanation

PBP2a (penicillin-binding protein 2a) is an alternative transpeptidase encoded by the mecA gene on SCCmec cassette. It has an extremely low affinity (high Km) for all beta-lactam antibiotics, meaning beta-lactams cannot bind and inhibit its cell-wall-synthesizing activity even at high drug concentrations. This structural alteration in the active site allows continued peptidoglycan cross-linking while all other native PBPs are inhibited. Beta-lactamase hydrolysis (option B) is a separate beta-lactam resistance mechanism found in MSSA and Gram-negatives; efflux and porin changes are mechanisms relevant to fluoroquinolone and carbapenem resistance in Gram-negatives.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.