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Antimicrobial Agents and Chemotherapy, August 2004, p. 2888-2896, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.2888-2896.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antibiotic-Inducible Promoter Regulated by the Cell Envelope Stress-Sensing Two-Component System LiaRS of Bacillus subtilis

Thorsten Mascher,{dagger} Sara L. Zimmer,{ddagger} Terry-Ann Smith,{ddagger} and John D. Helmann*

Department of Microbiology, Cornell University, Ithaca, New York 14853

Received 8 December 2003/ Returned for modification 27 February 2004/ Accepted 3 April 2004

Soil bacteria are among the most prodigious producers of antibiotics. The Bacillus subtilis LiaRS (formerly YvqCE) two-component system is one of several antibiotic-sensing systems that coordinate the genetic response to cell wall-active antibiotics. Upon the addition of vancomycin or bacitracin, LiaRS autoregulates the liaIHGFSR operon. We have characterized the promoter of the lia operon and defined the cis-acting sequences necessary for antibiotic-inducible gene expression. A survey for compounds that act as inducers of the lia promoter revealed that it responds strongly to a subset of cell wall-active antibiotics that interfere with the lipid II cycle in the cytoplasmic membrane (bacitracin, nisin, ramoplanin, and vancomycin). Chemicals that perturb the cytoplasmic membrane, such as organic solvents, are also weak inducers. Thus, the reporter derived from PliaI (the liaI promoter) provides a tool for the detection and classification of antimicrobial compounds.

* Corresponding author. Mailing address: Department of Microbiology, Wing Hall, Cornell University, Ithaca, NY 14853-8101. Phone: (607) 255-6570. Fax: (607) 255-3904. E-mail: jdh9{at}cornell.edu.

{dagger} Present address: Abteilung für Allgemeine Mikrobiologie, Institut für Mikrobiologie und Genetik, Georg-August-Universität, D-37077 Göttingen, Germany.

{ddagger} S.L.Z. and T.-A.S. contributed equally to this work.

Antimicrobial Agents and Chemotherapy, August 2004, p. 2888-2896, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.2888-2896.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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