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

Abstract

SummaryFarnesol 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 concentrations, suggesting that related compounds may participate in interspecies interactions with P. aeruginosa.

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

“…Farnesol (Table 3) is a signaling molecule produced by Candida albicans, an opportunistic fungal pathogen often found in mixed infections with P. aeruginosa in clinical settings. Farnesol-mediated inhibition of PQS production and PQS-controlled pyocyanin production was concentration dependent and was due to decreased expression of the pqs operon, which the authors propose to result from the farnseol-mediated formation of nonproductive interactions of the transcriptional regulator PqsR with the pqsA promoter (124). In addition, it was shown that naturally occurring levels of farnesol produced by C. albicans were sufficient to suppress PQS production during coculture, suggesting a physiologically relevant role for farnesol in modulation of PQS signaling.…”

“…In addition, it was shown that naturally occurring levels of farnesol produced by C. albicans were sufficient to suppress PQS production during coculture, suggesting a physiologically relevant role for farnesol in modulation of PQS signaling. Interestingly, other compounds containing the long-chain isoprenoid backbone were also able to repress PQS production, although to differing degrees, potentially providing a novel scaffold for the design of PQS synthesis inhibitors (124).…”

Future research trends in the major chemical language of bacteria

“…and a few animal pathogens, indicating that LuxS at large would have a metabolic role in other bacteria (Rezzonico and Duffy, 2008). Scientists are now also beginning to address the prospect of interspecies and interkingdom signaling using various signaling molecules among distantly related organisms which colonize similar niches (Cugini et al, 2007;. This signaling can lead to cooperation as well as competition/ inhibition.…”

Interspecies competition triggers virulence and mutability in Candida albicans–Pseudomonas aeruginosa mixed biofilms

“…Interestingly, in vitro studies have demonstrated that these signaling interactions between P. aeruginosa and C. albicans may in fact be bidirectional. It has been observed that the addition of farnesol leads to decreased Pseudomonas quinolone signal (PQS) production in P. aeruginosa and reduced levels of the PQS-regulated virulence factor pyocyanin (Cugini et al, 2007).…”