Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 26, Pages 17025-17030Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.252607699
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Antibiotics such as erythromycin and rifampicin, at low concentrations, alter global bacterial transcription patterns as measured by the stimulation or inhibition of a variety of promoter-lux reporter constructs in a Salmonella typhimurium library. Analysis of a 6,500-clone library indicated that as many as 5% of the promoters may be affected, comprising genes for a variety of functions, as well as a significant fraction of genes with no known function. Studies of a selection of the reporter clones showed that stimulation varied depending on the nature of the antibiotic, the promoter, and what culture medium was used; the response differed on solid as compared with liquid media. Transcription was markedly reduced in antibiotic-resistant hosts, but the presence of mutations deficient in stress responses such as SOS or universal stress did not prevent antibiotic-induced modulation. The results show that small molecules may have contrasting effects on bacteria depending on their concentration: either the modulation of bacterial metabolism by altering transcription patterns or the inhibition of growth by the inhibition of specific target functions. Both activities could play important roles in the regulation of microbial communities. These studies indicate that the detection of pharmaceutically useful natural product inhibitors could be effectively achieved by measuring activation of transcription at low concentrations in high-throughput assays using appropriate bacterial promoter-reporter constructs.
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