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Antimicrobial Agents and Chemotherapy, July 2004, p. 2588-2594, Vol. 48, No. 7
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.7.2588-2594.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Panel of Bacillus subtilis Reporter Strains Indicative of Various Modes of Action

Bernd Hutter,* Christina Fischer, Alexander Jacobi, Christoph Schaab, and Hannes Loferer*

GPC Biotech AG, Martinsried, Germany

Received 1 December 2003/ Returned for modification 21 February 2004/ Accepted 14 March 2004

In a recent project, we collected the transcriptional profiles of Bacillus subtilis 168 after treatment with a large set of diverse antibacterial agents. One result of the data analysis was the identification of marker genes that are indicative of certain compounds or compound classes. We cloned these promoter regions in front of a luciferase reporter gene and reintroduced the constructs individually into the B. subtilis chromosome. Strains were analyzed for their responsiveness after treatment with a set of 37 antibacterials. Twelve functional reporter strains were generated that were selectively and significantly upregulated by the compounds. The selectivity of the reporter strains ranged from generic pathways like protein biosynthesis, cell wall biosynthesis, and fatty acid biosynthesis to compound classes (quinolones and glycopeptides) and individual compounds (rifampin, cycloserine, and clindamycin). Five of the strains are amenable for high-throughput applications, e.g., pathway-specific screening. In summary, we successfully generated B. subtilis reporter strains that are indicative of the mechanisms of action of various classes of antibacterials. The set of reporter strains presented herein can be used for mode-of-action analyses and for whole-cell screening of compound libraries in a mode-of-action-specific manner.

* Corresponding author. Mailing address: GPC Biotech AG, Fraunhoferstr. 20, 82152 Martinsried/Munich, Germany. Phone: 49-89-8565-3233. Fax: 49-89-8565-2610. E-mail: bernd.hutter{at}gpc-biotech.com; hannes.loferer{at}gpc-biotech.com.

Antimicrobial Agents and Chemotherapy, July 2004, p. 2588-2594, Vol. 48, No. 7
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.7.2588-2594.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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