Hz. Zhang et al., A proteolytic transmembrane signaling pathway and resistance to beta-lactams in staphylococci, SCIENCE, 291(5510), 2001, pp. 1962-1965
beta -Lactamase and penicillin-binding protein Za mediate staphylococcal re
sistance to beta -lactam antibiotics, which are otherwise highly clinically
effective. Production of these inducible proteins is regulated by a signal
-transducing integral membrane protein and a transcriptional repressor. The
signal transducer is a fusion protein with penicillin-binding and zinc met
alloprotease domains. The signal for protein expression is transmitted by s
ite-specific proteolytic cleavage of both the transducer, which autoactivat
es, and the repressor, which is inactivated, unblocking gene transcription.
Compounds that disrupt this regulatory pathway could restore the activity
of beta -lactam antibiotics against drug-resistant strains of staphylococci
.