- The primary mechanism behind MRSA resistance to beta-lactam antibiotics is the alteration in penicillin-binding protein (PBP2a).
- This modified protein has a low affinity for beta-lactams, allowing MRSA to continue synthesizing its cell wall even in the presence of these antibiotics. Unlike typical PBPs, PBP2a is encoded by the mecA gene, which confers resistance by bypassing the inhibitory effects of beta-lactams.
- This mechanism is distinct from beta-lactamase production, making PBP2a alteration the critical factor in MRSA drug resistance.

Reference: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th Edition, Volume 2, Chapter 185