Characterization of the beta-lactam antibiotic sensor domain of the MecR1 signal sensor/transducer protein from methicillin-resistant Staphylococcus aureus

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved two mechanisms for resistance to beta-lactam antibiotics. One is production of a beta-lactamase, and the other is that of penicillin-binding protein 2a (PBP 2a). The expression of these two proteins is regulated by the bla and mec operons, respectively. BlaR1 and MecR1 are beta-lactam sensor/signal transducer proteins, which experience acylation by beta-lactam antibiotics on the cell surface and transduce the signal into the cytoplasm. The C-terminal surface domain of MecR1 (MecRS) has been cloned, expressed, and purified to homogeneity. This protein has been characterized by documenting that it has a critical and unusual Nzeta-carboxylated lysine at position 394. Furthermore, the kinetics of interactions with beta-lactam antibiotics were evaluated, a process that entails conformational changes for the protein that might be critical for the signal transduction event. Kinetics of acylation of MecRS are suggestive that signal sensing may be the step where the two systems are substantially different from one another.