RT Journal
A1 Fischer, Hans Peter
A1 Brunner, Nina A.
A1 Wieland, Bernd
A1 Paquette, Jesse
A1 Macko, Ludwig
A1 Ziegelbauer, Karl
A1 Freiberg, Christoph
T1 Identification of Antibiotic Stress-Inducible Promoters: A Systematic Approach to Novel Pathway-Specific Reporter Assays for Antibacterial Drug Discovery
JF Genome Research 
JO Genome Research 
YR 2004 
FD January 01 
VO 14 
IS 1 
SP 90 
OP 98 
DO 10.1101/gr.1275704 
UL http://genome.cshlp.org/content/14/1/90.abstract 
AB As present antibiotics therapy becomes increasingly ineffectual, new technologies are required to identify and develop novel classes of antibacterial agents. An attractive alternative to the classical target-based approach is the use of promoter-inducible reporter assays for high-throughput screening. The wide usage of these assays is, however, limited by the small number of specifically responding promoters that are known at present. This work describes a novel approach for identifying genetic regulators that are suitable for the design of pathway-specific assays. The basis for the proposed strategy is a large set of antibiotics-triggered expression profiles (“Reference Compendium”). Pattern recognition algorithms applied to the expression data pinpoint the relevant transcription-factor-binding sites in whole-genome sequences. Using this technique, we constructed a fatty-acid-pathway-specific reporter assay that is based on a novel stress-inducible promoter. In a proof-of-principle experiment, this assay was shown to enable screening for new small-molecule inhibitors of bacterial growth.