Methicillin-resistant
Staphylococcus aureus (MRSA) has evolved two me
chanisms for resistanceto
![](/images/gif<font color=)
chars/beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics. One is production of a
![](/images/gif<font color=)
chars/beta2.gif" BORDER=0 ALIGN="middle">-lactamase, and the other is that of penicillin-bindingprotein 2a (PBP 2a). The expression of these two proteins is regulated by the
bla and
mec operons,respectively. BlaR1 and MecR1 are
![](/images/gif<font color=)
chars/beta2.gif" BORDER=0 ALIGN="middle">-lactam sensor/signal transducer proteins, which experience acylationby
![](/images/gif<font color=)
chars/beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics on the cell surface and transduce the signal into the cytoplasm. The C-terminalsurface domain of MecR1 (MecR
S) has been cloned, expressed, and purified to homogeneity. This proteinhas been
characterized by documenting that it has a critical and unusual
N
chars/zeta.gif" BORDER=0 >-carboxylated lysine at position394. Furthermore, the kinetics of interactions with
![](/images/gif<font color=)
chars/beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics were evaluated, a process thatentails conformational
changes for the protein that might be critical for the signal transduction event.Kinetics of acylation of MecR
S are suggestive that signal sensing may be the step where the two systemsare substantially different from one another.