Correlation between regulation of mecA transcription and expression of methicillin resistance in staphylococci

Total RNA was used to study the effect of penicillinase plasmid pI524 and of mecR, the regulatory region located on the methicillin resistance determinant (mec), on the expression of mecA, the gene coding for the low-affinity penicillin-binding protein PBP2', in methicillin-resistant staphylococci. In the present report, we show that the regulation of methicillin resistance occurs primarily at the level of mecA transcription and that in the presence of intact plasmid pI524 or mecR, the gene undergoes negative control. The relative amount of mecA mRNA present during exponential growth in uninduced cultures matches the type of mecA regulation and decreases in the following order: constitutive greater than pI524 greater than mecR-dependent mecA expression. Induction of mecA by methicillin is faster in pI524- than in mecR-controlled strains. The overall mRNA half-life is similar for all strains analyzed. Our results indicate that methicillin resistance under mecR control in certain staphylococcal strains could escape detection by the standard disk diffusion test and broth microdilution test because of the very slow derepression of the mecA gene. This finding is of importance for the clinical detection of this type of methicillin resistance.