Effect of NaCl and nafcillin on penicillin-binding protein 2a and heterogeneous expression of methicillin resistance in Staphylococcus aureus

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Abstract
Expression of methicillin resistance in heterogeneous strains of Staphylococcus aureus is enhanced by 2 to 5% NaCl in the medium and by selection with beta-lactam antibiotics. Resistance is associated with production of a penicillin-binding protein (PBP), PBP 2a, with low affinity for binding beta-lactam antibiotics. Therefore, the effects of NaCl and nafcillin on amounts of PBP 2a produced and its binding affinity were examined and correlated with expression of resistance. Nafcillin-triggered autolysis also was examined. No relationships between the level of resistance expressed and (i) relative amounts of PBP 2a, (ii) inducibility of PBP 2a by nafcillin, or (iii) binding affinity of nafcillin for PBP 2a were found. A protective effect of NaCl for the susceptible subpopulation, corresponding to inhibition of autolysis, was observed for heterogeneous strains. Even in the absence of NaCl, highly resistant cells were relatively tolerant to nafcillin-triggered autolysis. These results support the hypothesis that high levels of resistance require an additional factor besides PBP 2a. This factor may act within the autolytic pathway.