How is MRSA resistance to beta-lactams determined?

The resistance of Methicillin-resistant Staphylococcus aureus (MRSA) to beta-lactams, including methicillin and other penicillin derivatives, primarily stems from the production of modified penicillin-binding proteins (PBPs). In MRSA, the mecA gene encodes a variant of PBP, known as PBP2a, which has a significantly lower affinity for beta-lactam antibiotics. This change enables MRSA to continue synthesizing its cell wall even in the presence of these antibiotics, rendering them ineffective.

While the presence of beta-lactamase enzymes can also confer resistance to some other beta-lactam antibiotics by degrading them, it is not the primary mechanism of resistance in MRSA. Additionally, alterations in bacterial ribosomes and modifications of cell wall synthesis do not typically play a direct role in the specific beta-lactam resistance seen in MRSA. The key factor is truly the modification of the penicillin-binding proteins, which allows these bacteria to bypass the action of beta-lactam antibiotics.