A hierarchical quorum‐sensing cascade in Pseudomonas aeruginosa links the transcriptional activators LasR and RhIR (VsmR) to expression of the stationary‐phase sigma factor RpoS

Abstract

In Pseudomonas aeruginosa, the production of many virulence factors and secondary metabolites is regulated in concert with cell density through quorum sensing. Two quorum-sensing regulons have been identified in which the LuxR homologues LasR and RhlR are activated by N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-butanoyl-L-homoserine lactone (BHL) respectively. The lasR and rhlR genes are linked to the luxl homologues lasl and rhll, which are responsible for synthesis of OdDHL and BHL, respectively. As lasRl and rhlRl are both involved in regulating synthesis of exoenzymes such as elastase, we sought to determine the nature of their interrelationship. By using lacZ transcriptional fusions in both homologous (P. aeruginosa) and heterologous (Escherichia coli) genetic backgrounds we provide evidence that (i) lasR is expressed constitutively throughout the growth cycle, (ii) rhlR expression is regulated by LasR/OdDHL, and (iii) that RhlR/BHL regulates rhll. We also show that expression of the stationary-phase sigma factor gene rpoS is abolished in a P. aeruginosa lasR mutant and in the pleiotropic BHL-negative mutant PANO67. Furthermore, our data reveal that kin E. coli, an rpoS-lacZ fusion is regulated directly by RhlR/BHL. Taken together, these results indicate that P. aeruginosa employs a multilayered hierarchical quorum-sensing cascade involving RhlR/BHL and LasR/OdDHL, interlinked via RpoS, to integrate the regulation of virulence determinants and secondary metabolites with adaptation and survival in the stationary phase.

Bacterial cell‐to‐cell signaling promotes the evolution of resistance to parasitic bacteriophages

“…The lack of signal effect can be most likely attributed to the experimental environment, which did not favor QS‐signaling: Resources are readily available in KB media (Friman et al., 2013) and the QS expression thus unlikely offered any additional benefits for the signaling bacteria. It is known that knocking out the las system will have downstream effects on the rhl system (Latifi et al., 1996), and as a result, it is often thought that the las mutants behave similarly as the rhl mutants. However, it has also been shown that las and rhl systems can be decoupled and that the interactions between different QS systems depend on the environmental conditions (Diggle et al., 2003).…”

Acyl-homoserine lactone-dependent eavesdropping promotes competition in a laboratory co-culture model

“…Because of the signal diffusibility, AHLs must reach a critical environmental concentration before they cause changes in gene expression. It is common that the AHL synthase gene is among the genes activated, creating a positive feedback loop that results in increased production of signal (Engebrecht et al, 1983;Seed et al, 1995;Latifi et al, 1996;Duerkop et al, 2009;Stauff and Bassler, 2011). Thus, AHL signaling can coordinate population-wide changes in a celldensity-dependent manner.…”

Quorum quenching enzyme activity is widely conserved in the sera of mammalian species

“…The opportunistic pathogen Pseudomonas aeruginosa produces two AHLs, N-(3-oxododecanoyl)-L L-homoserine lactone (3OC12HSL) and N-butanoyl-L L-homoserine lactone (C4HSL), which control production of extracellular virulence factors and biofilm formation [3][4][5][6][7]. Production of these AHLs is hierarchically regulated in which threshold levels of 3OC12HSL are required to activate the synthesis of C4HSL [6,7]. Considerable attention has been directed at developing anti-quorum-sensing agents as possible infection control therapeutics [8][9][10].…”