Genomic Investigation of the Role of Antibiotics As Signal Molecules in Pseudomonas aeruginosa

Antibiotics have recently been shown to play a role as signaling molecules besides bacterial killing or growth inhibition. To understand antibiotic regulatory networks in bacteria, we investigated Pseudomonas aeruginosa gene expression profiles in response to subinhibitory concentrations of six antibiotics (ampicilin, kanamycin, chloramphenicol, tetracycline, erythromycin, ciprofloxacin) by using a random promoter-luxCDABE reporter fusion library. Both common and unique responses to different antibiotics were observed, suggesting existence of both shared and unique regulatory pathways in P. aeruginosa. Total of 48 promoter clones were selected and further tested. They were regulated at least two-fold by at least one of the antibiotics. Among them, 17 promoters and the genes or operons driven by them activated by at least four antibiotics were identified by sequencing analysis. These genes/operons encode potential transcriptional regulators, components of ABC transporters, or unknown proteins. These results extended our knowledge of the global effect of antibiotics as signal molecules on gene expression, and the potential components of the genetic regulatory networks identified should facilitate further studies.