Farnesol, a common sesquiterpene, inhibits PQS production in Pseudomonas aeruginosa

• Published in: Molecular microbiology Vol. 65; no. 4; pp. 896 - 906
• Main Authors: Cugini, Carla, Calfee, M. Worth, Farrow, John M. III, Morales, Diana K, Pesci, Everett C, Hogan, Deborah A
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.08.2007; Blackwell Publishing Ltd; Blackwell Science
• Subjects: Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - metabolism; Electrophoretic Mobility Shift Assay; Escherichia coli; Escherichia coli - drug effects; Farnesol - chemistry; Farnesol - pharmacology; Fundamental and applied biological sciences. Psychology; Fungi; Gene Expression Regulation, Bacterial - drug effects; Genes; Microbiology; Miscellaneous; Molecular biology; Molecules; Promoter Regions, Genetic - genetics; Protein Binding - drug effects; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - growth & development; Pseudomonas aeruginosa - metabolism; Pyocyanine - biosynthesis; Quinolones - metabolism; Recombinant Fusion Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription, Genetic - drug effects; Pseudomonadales; Bacteria; Pseudomonadaceae; Pseudomonas aeruginosa; Sesquiterpenes
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2007.05840.x

Farnesol is a sesquiterpene produced by many organisms, including the fungus Candida albicans. Here, we report that the addition of farnesol to cultures of Pseudomonas aeruginosa, an opportunistic human bacterial pathogen, leads to decreased production of the Pseudomonas quinolone signal (PQS) and the PQS-controlled virulence factor, pyocyanin. Within 15 min of farnesol addition, decreased transcript levels of pqsA, the first gene in the PQS biosynthetic operon, were observed. Transcript levels of pqsR (mvfR), which encodes the transcription factor that positively regulates pqsA, were unaffected. An Escherichia coli strain producing PqsR and containing the pqsA promoter fused to lacZ similarly showed that farnesol inhibited PQS-stimulated transcription. Electrophoretic mobility shift assays showed that, like PQS, farnesol stimulated PqsR binding to the pqsA promoter at a previously characterized LysR binding site, suggesting that farnesol promoted a non-productive interaction between PqsR and the pqsA promoter. Growth with C. albicans leads to decreased production of PQS and pyocyanin by P. aeruginosa, suggesting that the amount of farnesol produced by the fungus is sufficient to impact P. aeruginosa PQS signalling. Related isoprenoid compounds, but not other long-chain alcohols, also inhibited PQS production at micromolar concen-trations, suggesting that related compounds may participate in interspecies interactions with P. aeruginosa.