(a) Induction of staphylococcal β-lactamase synthesis in the presence of the β-lactam antibiotic penicillin. I. The DNA-binding protein BlaI binds to the operator region, thus repressing RNA transcription from both blaZ and blaR1-blaI. In the absence of penicillin, β-lactamase is expressed at low levels. II. Binding of penicillin to the transmembrane sensor-transducer BlaR1 stimulates BlaR1 autocatalytic activation. III–IV. Active BlaR1 either directly or indirectly (via a second protein, BlaR2) cleaves BlaI into inactive fragments, allowing transcription of both blaZ and blaR1-blaI to commence. V–VII. β-Lactamase, the extracellular enzyme encoded by blaZ (V), hydrolyzes the β-lactam ring of penicillin (VI), thereby rendering it inactive (VII). (b) Mechanism of S. aureus resistance to methicillin. Synthesis of PBP2a proceeds in a fashion similar to that described for β-lactamase. Exposure of MecR1 to a β-lactam antibiotic induces MecR1 synthesis. MecR1 inactivates MecI, allowing synthesis of PBP2a. MecI and BlaI have coregulatory effects on the expression of PBP2a and β-lactamase.