mecA is under the control of two regulatory genes, mecI and mecR1. MecI is usually bound to the mecA promoter and functions as a repressor. In the presence of a β-lactam antibiotic, MecR1 initiates a signal transduction cascade that leads to transcriptional activation of mecA. This is achieved by MecR1-mediated cleavage of MecI, which alleviates MecI repression. mecA is further controlled by two co-repressors, blaI and blaR1. blaI and blaR1 are homologous to mecI and mecR1, respectively, and normally function as regulators of blaZ, which is responsible for penicillin resistance. The DNA sequences bound by mecI and blaI are identical; therefore, blaI can also bind the mecA operator to repress transcription of mecA.
