1887

Abstract

has been previously shown to stimulate the production of phenazine toxins in dual-species colony biofilms. Here, we report that mutants, which lack the master quorum sensing system regulator, regain the ability to produce quorum-sensing-regulated phenazines when cultured with . Farnesol, a signalling molecule produced by , was sufficient to stimulate phenazine production in LasR laboratory strains and clinical isolates. Δ mutants are defective in production of the quinolone signal (PQS) due to their inability to properly induce , which encodes the enzyme necessary for the last step in PQS biosynthesis. We show that expression of in a Δ strain was sufficient to restore PQS production, and that farnesol restored expression in Δ mutants. The farnesol-mediated increase in required RhlR, a transcriptional regulator downstream of LasR, and farnesol led to higher levels of -butyryl-homoserine lactone, the small molecule activator of RhlR. Farnesol promotes the production of reactive oxygen species (ROS) in a variety of species. Because the antioxidant -acetylcysteine suppressed farnesol-induced RhlR activity in LasR strains, and hydrogen peroxide was sufficient to restore PQS production in mutants, we propose that ROS are responsible for the activation of downstream portions of this quorum sensing pathway. LasR mutants frequently arise in the lungs of patients chronically infected with . The finding that , farnesol or ROS stimulate virulence factor production in strains provides new insight into the virulence potential of these strains.

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2010-10-01
2019-09-18
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