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Prediction of mechanisms of action of antibacterial compounds by gene expression profiling
Author(s): Hutter B, Schaab C, Albrecht S, Borgmann M, Brunner NA, Freiberg C, Ziegelbauer K, Rock CO, Ivanov I, Loferer H
Source: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY    Volume: 48    Issue: 8    Pages: 2838-2844    Published: AUG 2004  
Times Cited: 54     References: 34     
Abstract: We have generated a database of expression profiles carrying the transcriptional responses of the model organism Bacillus subtilis following treatment with 37 well-characterized antibacterial compounds of different classes. The database was used to build a predictor for the assignment of the mechanisms of action (MoAs) of antibacterial compounds by the use of support vector machines. This predictor was able to correctly classify the MoA class for most compounds tested. Furthermore, we provide evidence that the in vivo MoA of hexachlorophene does not match the MoA predicted from in vitro data, a situation frequently faced in drug discovery. A database of this kind may facilitate the prioritization of novel antibacterial entities in drug discovery programs. Potential applications and limitations are discussed.
Document Type: Article
Language: English
Reprint Address: Loferer, H (reprint author), GPC Biotech AG, Fraunhoferstr 20, D-8152 Munich, Germany
Addresses:
1. GPC Biotech AG, D-8152 Munich, Germany
2. Bayer AG, Wuppertal, Germany
3. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA
Publisher: AMER SOC MICROBIOLOGY, 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
Subject Category: Microbiology; Pharmacology & Pharmacy
IDS Number: 842IV
ISSN: 0066-4804
DOI: 10.1128/AAC.48.8.2838-2844.2004
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