Natural methicillin resistance in comparison with that selected by in-vitro drug exposure in Staphylococcus aureus

Methicillin resistant staphylococci selected during serial passage in increasing concentrations of methicillin were compared with an isogenic methicillin resistant strain carrying the methicillin resistance determinant (mec) found in clinical isolates of Staphylococcus aureus. Selection for methicillin resistance was followed by changes in the binding characteristic of penicillin binding proteins (PBPs) 2 and 4. There was no immunological nor genetic relationship between the mec-determined low affinity PBP2' and the PBPs of the in-vitro selected mutants. The Tn551 insertion omega 2003, which inactivates mec determined methicillin resistance, but which is not linked to mec, also partially reduced in-vitro selected methicillin resistance. This suggests that this methicillin resistance controlling factor contributes at least partially to methicillin resistance selected in vitro.