Mechanism of beta-lactam-resistance in methicillin-resistant Staphylococcus aureus

The role of penicillin-binding protein (PBP) 2' in the expression of beta-lactam-resistance was investigated using methicillin-resistant Staphylococcus aureus (MRSA) strains with different level of resistance. Both high- and moderate-level MRSA produced very similar PBP 2' with low affinities for beta-lactam antibiotics. Affinities of antibiotics for PBP 2' (I50, concentration which inhibits [14C] benzylpenicillin-binding by 50%) correlated well with their antibacterial activities (MIC) in a high-level MRSA, but did not in a moderate-level MRSA. High-level MRSA contained a larger amount of PBP 2' than moderate-level MRSA, and the amount of PBP 2' decreased by increasing the temperature of the culture; the extent of decrease was larger in a strain which was sensitive at 37 degrees C than a strain which exerted relatively high level resistance even at 40 degrees C. A cephamycin-resistant, methicillin-sensitive strain began to synthesize PBP 2' by adding cephamycin-type antibiotics to the medium and consequently acquired resistance to methicillin. Latent MRSA producing no PBP 2' generated clones which produced PBP 2' constitutively and were highly resistant to all beta-lactams. These results suggest that the presence of PBP 2' is critical for the expression of beta-lactam-resistance in MRSA and the degree of the resistance depends mainly on the amount of PBP 2' which differs from strain to strain and is influenced by environments such as temperature and the presence of inducer.