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Science 291 (5510): 1962-1965

Copyright © 2001 by the American Association for the Advancement of Science

A Proteolytic Transmembrane Signaling Pathway and Resistance to beta -Lactams in Staphylococci

H. Z. Zhang, C. J. Hackbarth, K. M. Chansky, H. F. Chambers*

beta -Lactamase and penicillin-binding protein 2a mediate staphylococcal resistance 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 metalloprotease domains. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which autoactivates, 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.

Division of Infectious Diseases, San Francisco General Hospital, Department of Medicine, University of California at San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
*   To whom correspondence should be addressed. E-mail: chipc{at}itsa.ucsf.edu

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