Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors

Dekimpe, Valérie; Déziel, Éric

doi:10.1099/mic.0.022764-0

Cited by 260 publications

(255 citation statements)

References 89 publications

(112 reference statements)

Supporting

Mentioning

224

Contrasting

Unclassified

Order By: Relevance

“…6), suggesting that during anaerobic growth, PAI-2-mediated QS may play a more important role than QS induced by the action of other signaling molecules. It was recently reported that PAI-2 production, albeit delayed, still occurs in a lasR mutant strain and that the RhlI/R QS system can override, at least in part, the effects of lasR mutations (13). In addition, comprehensive chronological genetic analysis using a large number of CF isolates revealed that isolates that lost the ability to produce PAI-1 appeared earlier than strains that were unable to produce both PAI-1 and PAI-2 (2).…”

Section: Discussionmentioning

confidence: 99%

Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa

et al. 2011

View full text Add to dashboard Cite

Pseudomonas aeruginosa, an opportunistic pathogen of clinical importance, causes chronic airway infections in patients with cystic fibrosis (CF). Current literature suggests that pockets with reduced oxygen tension exist in the CF airway mucus. However, virulence features of this opportunistic pathogen under such conditions are largely unknown. Cell-free supernatant of the standard laboratory P. aeruginosa strain PAO1 obtained from anaerobic culture, but not aerobic culture, failed to kill A549 human airway epithelial cells. Further investigation revealed that this reduced cytotoxicity upon anaerobiosis was due to the suppressed secretion of elastase, a virulence factor controlled by P. aeruginosa quorum sensing (QS). Both a lacZ-reporter fusion assay and quantitative real-time PCR (RT-PCR) analysis demonstrated that transcription of the elastase-encoding lasB gene was substantially decreased during anaerobic growth compared with aerobic growth. Moreover, transcription of other genes controlled by the LasI/R QS system, such as rhlR, vqsR, mvfR, and rsaL, was also repressed under the same anaerobic growth conditions. Importantly, synthesis of 3-oxo-C 12 -HSL (PAI-1), an autoinducer molecule that mediates induction of the LasI/R QS system, was >22-fold decreased during anaerobic growth while C 4 -HSL (PAI-2), which mediates RhlI/R QS, was nondetectable under the same growth conditions. Transcription of the lasB gene was restored by exogenous supplementation with autoinducers, with PAI-2 more effective than PAI-1 or Pseudomonas quinolone signal (PQS) at restoring transcription of the lasB gene. Together, these results suggest that anaerobiosis deprives P. aeruginosa of the ability to regulate its virulence via QS and this misregulation attenuates the pathogenic potential of this important pathogen.

show abstract

Section: Discussionmentioning

confidence: 99%

Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Addition of the LasI-generated signal to a signal synthesis mutant only induced expression by 1.6-fold, but addition of both acyl-HSL signals induced expression by ninefold (Schuster et al, 2003). Thus, it was conceivable that lasR affected dipeptide transport and processing mainly indirectly, through its effect on the rhl system, although this regulation is nutritionally conditional (Medina et al, 2003;Dekimpe and Deziel, 2009;Mellbye and Schuster, 2014). To investigate a possible link between QS and dipeptide metabolism in our experimental system, we quantified the transcript levels of dppA3 and mdpA during growth in CAA medium for our set of eight P. aeruginosa strains used in the previous sections.…”

Section: Transcriptional Regulation Of Dipeptide Transport and Procesmentioning

confidence: 99%

Non-social adaptation defers a tragedy of the commons in Pseudomonas aeruginosa quorum sensing

et al. 2015

View full text Add to dashboard Cite

In a process termed quorum sensing (QS), the opportunistic bacterial pathogen Pseudomonas aeruginosa uses diffusible signaling molecules to regulate the expression of numerous secreted factors or public goods that are shared within the population. But not all cells respond to QS signals. These social cheaters typically harbor a mutation in the QS receptor gene lasR and exploit the public goods produced by cooperators. Here we show that non-social adaptation under growth conditions that require QS-dependent public goods increases tolerance to cheating and defers a tragedy of the commons. The underlying mutation is in the transcriptional repressor gene psdR. This mutation has no effect on public goods expression but instead increases individual fitness by derepressing growth-limiting intracellular metabolism. Even though psdR mutant populations remain susceptible to invasion by isogenic psdR lasR cheaters, they bear a lower cheater load than do wild-type populations, and they are completely resistant to invasion by lasR cheaters with functional psdR. Mutations in psdR also sustain growth near wild-type levels when paired with certain partial loss-offunction lasR mutations. Targeted sequencing of multiple evolved isolates revealed that mutations in psdR arise before mutations in lasR, and rapidly sweep through the population. Our results indicate that a QS-favoring environment can lead to adaptations in non-social, intracellular traits that increase the fitness of cooperating individuals and thereby contribute to population-wide maintenance of QS and associated cooperative behaviors.

show abstract

“…LasR and RhlR, in complex with their respective acyl-HSL signals, control the expression of over 300 genes (Hentzer et al, 2003;Schuster et al, 2003;Wagner et al, 2003). The las system controls activation of the rhl system (Latifi et al, 1996;Pesci et al, 1997), but this regulatory hierarchy is nutritionally conditional (Medina et al, 2003;Dekimpe and Deziel, 2009).…”

Section: Introductionmentioning

confidence: 99%

Negative regulation of bacterial quorum sensing tunes public goods cooperation

Gupta

Schuster

2013

The ISME Journal

View full text Add to dashboard Cite

Bacterial quorum sensing (QS) often coordinates the expression of other, generally more costly public goods involved in virulence and nutrient acquisition. In many Proteobacteria, the basic QS circuitry consists of a synthase that produces a diffusible acyl-homoserine lactone and a cognate receptor that activates public goods expression. In some species, the circuitry also contains negative regulators that have the potential to modulate the timing and magnitude of activation. In this study, we experimentally investigated the contribution of this regulatory function to the evolutionary stability of public goods cooperation in the opportunistic pathogen Pseudomonas aeruginosa. We compared fitness and public goods expression rates of strains lacking either qteE or qscR, each encoding a distinct negative regulator, with those of the wild-type parent and a signalblind receptor mutant under defined growth conditions. We found that (1) qteE and qscR mutations behave virtually identically and have a stronger effect on the magnitude than on the timing of expression, (2) high expression in qteE and qscR mutants imposes a metabolic burden under nutrient conditions that advance induction and (3) high expression in qteE and qscR mutants increases population growth when QS is required, but also permits invasion by both wild-type and receptor mutant strains. Our data indicate that negative regulation of QS balances the costs and benefits of public goods by attenuating expression after transition to the induced state. As the cells cannot accurately assess the amount of cooperation needed, such bet-hedging would be advantageous in changing parasitic and nonparasitic environments.

show abstract

Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors

Cited by 260 publications

References 89 publications

Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa

Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa

Non-social adaptation defers a tragedy of the commons in Pseudomonas aeruginosa quorum sensing

Negative regulation of bacterial quorum sensing tunes public goods cooperation

Contact Info

Product

Resources

About