Quinolone signaling in the cell-to-cell communication system of <i>Pseudomonas</i> <i>aeruginosa</i>

TLDR

Quorum sensing in Gram‑negative bacteria, including Pseudomonas aeruginosa, uses homoserine lactone autoinducers to regulate virulence gene expression via the las and rhl systems. The study identifies 2‑heptyl‑3‑hydroxy‑4‑quinolone (PQS) as a novel Pseudomonas aeruginosa signal that regulates lasB expression and whose production and activity depend on the las and rhl quorum‑sensing systems, demonstrating that cell‑to‑cell communication extends beyond acyl‑homoserine lactones.

Abstract

Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa , which contains two quorum sensing systems ( las and rhl ) that operate via the autoinducers, N -(3-oxododecanoyl)- l -homoserine lactone and N -butyryl- l -homoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB , which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones.