QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas aeruginosa

Abstract

The opportunistic pathogenic bacterium Pseudomonas aeruginosa uses quorum-sensing signaling systems as global regulators of virulence genes. There are two quorum-sensing signal receptor and signal generator pairs, LasR-LasI and RhlR-RhlI. The recently completed P. aeruginosa genome-sequencing project revealed a gene coding for a homolog of the signal receptors, LasR and RhlR. Here we describe a role for this gene, which we call qscR. The qscR gene product governs the timing of quorum-sensing-controlled gene expression and it dampens virulence in an insect model. We present evidence that suggests the primary role of QscR is repression of lasI. A qscR mutant produces the LasI-generated signal prematurely, and this results in premature transcription of a number of quorum-sensing-regulated genes. When fed to Drosophila melanogaster, the qscR mutant kills the animals more rapidly than the parental P. aeruginosa. The repression of lasI by QscR could serve to ensure that quorum-sensing-controlled genes are not activated in environments where they are not useful.

Cell-signalling repression in bacterial quorum sensing

“…For general parameter values it is not possible to determine the sign of ∂T E /∂R 0 . However, in the biologically appropriate regime k d k u , we have ∂T E /∂R 0 > 0; hence increasing the QSE inhibitor concentration will, as is to be expected, prolong the timescale for up regulation (this is in agreement with the experimental results of Chugani et al [6]). Furthermore, we have ∂a * E /∂R 0 < 0 and ∂N * E /∂R 0 < 0, so increasing R 0 reduces QSM build up and the up-regulated cell fraction.…”

“…Discoveries in recent years have shown that a few species have evolved means of bypassing this problem, by repressing certain components of the QS process. The most well studied examples are those of P. aeruginosa [6,7,8,21] and A. tumefaciens [4,23]. The repression mechanisms investigated in this paper are summarised below, the first two being known to be relevant for P. aeruginosa and the last to A. tumefaciens.…”

“…"Background" Inhibition (BI) of QSM output by constitutively produced regulator proteins which interfere in some way with the production or action of the QSE (which catalyses the reaction of the QSM precursors). Two such proteins have been identified in P. aeruginosa, namely QscR [6] and RsmA [21], which are produced independently of QS; see Figure 1. RsmA is believed to destroy messenger-RNA transcripts for many proteins [13], including that for the enzyme LasI, the QSE for the QSM 3-oxo-C12-HSL in P. aeruginosa (see Figure 2); how QscR inhibit QSM output is currently unknown.…”

How Drosophila combats microbial infection: a model to study innate immunity and host–pathogen interactions

“…P. aeruginosa has previously been shown to be highly pathogenic to Drosophila [71], and it is now the focus of several groups that use Drosophila as an alternative model system to study this important pathogen. Drosophila can be used to screen for P. aeruginosa mutants with reduced virulence and to analyse the complex interactions between this bacterium and the innate host defence response [72,73].…”

Biofilm : mise en place et organisation d’une communauté bactérienne

“…Le gène de type « I » est un de ces gènes cibles et les molécules d'HSL sont appelées auto-inducteurs. À ce jour, trois systèmes de type quorum sensing ont été caractérisés chez P. aeruginosa, il s'agit de lasR/lasI, REVUES SYNTHÈSE rhlR/rhlI et qscR [15,16]. Ces systèmes sont connectés au sein d'une cascade et contrôlent l'expression de la quasitotalité des gènes impliqués dans la virulence.…”