Suppression of methicillin resistance in a mecA-containing pre-methicillin-resistant Staphylococcus aureus strain is caused by the mecI-mediated repression of PBP 2' production.

The mechanism of methicillin susceptibility was studied in Staphylococcus aureus N315P, a pre-methicillin-resistant S. aureus strain that is susceptible to methicillin, despite the presence of mecA in the chromosome. In the presence of mec regulator genes mecI and mecR1, transcription of the mecA gene was not inducible by the addition of methicillin to the culture medium. Inactivation of the mecI gene function by replacing it with tetL made N315P express heterogeneous-type methicillin resistance. The subclone, in which the mecI gene was replaced, subclone P delta I, produced 12 times greater amounts of mecA gene transcripts and 8.5 times more PBP 2' protein than N315P. These data indicate that the mecI gene-encoded repression of mecA gene transcription is responsible for the apparent methicillin susceptibility phenotype of pre-methicillin-resistant S. aureus N315P.