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Recently, we have demonstrated that the cognate regulatory locus of the mecA gene in methicillin-resistant Staphylococcus aureus (MRSA) is in fact a three-component system containing the novel mecR2 gene coding for an antirepressor. MecR2 interacts with the repressor MecI, disturbing its binding to the mecA promoter and fostering its proteolysis. Here, we engineered a point mutation in the putative cleavage site of MecI and demonstrated that MecI proteolysis is strictly required for the optimal expression of β-lactam resistance.

Proteolysis of mecA Repressor Is Essential for Expression of Methicillin Resistance by Staphylococcus aureus