Global position analysis of the <i>Pseudomonas aeruginosa</i> quorum‐sensing transcription factor LasR

Gilbert, Kerrigan B.; Kim, Tae Hoon; Gupta, Rashmi; Greenberg, E. Peter; Schuster, Martín

doi:10.1111/j.1365-2958.2009.06832.x

Cited by 207 publications

(228 citation statements)

References 70 publications

(150 reference statements)

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“…LasR, the most upstream QS regulon in the P. aeruginosa QS hierarchy, regulates the expression of more than 300 virulenceassociated genes (17). However, recent genetic studies using diverse P. aeruginosa clinical isolates reported that adaptive mutations in the lasR gene occur spontaneously in the course of chronic airway infection in CF (9,12,19,42).…”

Section: Discussionmentioning

confidence: 99%

“…Next, we sought to elucidate the effect of suppressed synthesis of PAI-1 and PAI-2 on the expression of downstream virulence genes. We tested eight genes reported to be directly regulated by LasR (17). Figure 5A shows the relative expression of these selected genes as measured by quantitative RT-PCR analysis.…”

Section: Vol 79 2011 Suppressed Qs In P Aeruginosa During Anaerobimentioning

confidence: 99%

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

et al. 2011

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Vol 79 2011 Suppressed Qs In P Aeruginosa During Anaerobimentioning

confidence: 99%

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

et al. 2011

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“…When LasR/3O-C12-HSL binding to DNA was studied in vivo by immunoprecipitation of chromatin, a third las box was described (Gilbert et al, 2009). This las box (rhlR-3 las box, Fig.…”

Section: Lasr-binding Sequences Overlap Vbs1 and Vbs2mentioning

confidence: 99%

“…LasR/3-O-C12-HSL transcriptional regulation of rhlR was shown to be due to its activation of promoter 1 through its binding to a las box (the rhlR-1 las box), and possibly also of promoter 4 (Medina et al, 2003a). A second LasR/3O-C12-HSL-binding site was identified upstream of rhlR promoter 1 by the analysis of DNA sequences after immunoprecipitation of DNA-LasR complexes (Gilbert et al, 2009). Transcription initiation at promoter 2 was shown to be constitutive.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of Pseudomonas aeruginosa rhlR: role of the CRP orthologue Vfr (virulence factor regulator) and quorum-sensing regulators LasR and RhlR

et al. 2011

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The production of many virulence factors by Pseudomonas aeruginosa is regulated by the quorum-sensing (QS) response. In this regulatory network LasR and RhlR, bound to their corresponding autoinducers, play a central role. The QS response has a hierarchical structure: LasR/3O-C12-HSL activates the transcription of rhlR, and RhlR/C4-HSL activates the transcription of several genes, including the rhlAB operon, which encodes the enzymes responsible for rhamnolipid synthesis. The rhlAB operon is located immediately upstream of the rhlR gene. rhlR has four transcription start sites, two of which are located in the rhlB coding region. Vfr directly activates transcription of lasR, and has been reported to be also involved in rhlR expression. The aim of this work was to characterize the details of the mechanism of rhlR transcriptional regulation. We show that Vfr directly regulates rhlR transcription through its binding to several Vfr-binding sites (VBSs) present in the rhlR promoter region, one of which has a negative effect on transcription. Two of the VBSs overlap with las boxes where LasR/3O-C12-HSL binds to activate rhlR transcription. We also show that rhlR transcription is subject to positive-feedback autoregulation through RhlR/C4-HSL activation of the rhlA promoter. This positive autoregulation plays a major role in rhlR expression.

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“…Its transcription appears to be activated by LasR (Gilbert et al, 2009), and it is thought to function analogously to the QS antiactivator TraM in Agrobacterium tumefaciens (Fuqua et al, 1995;Piper and Farrand, 2000). QteE represses the expression of several las and rhl-dependent target genes by independently reducing LasR and RhlR protein stability, probably through direct protein-protein interaction (Siehnel et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Negative regulation of bacterial quorum sensing tunes public goods cooperation

Gupta

Schuster

2013

The ISME Journal

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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.

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Global position analysis of the Pseudomonas aeruginosa quorum‐sensing transcription factor LasR

Cited by 207 publications

References 70 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

Transcriptional regulation of Pseudomonas aeruginosa rhlR: role of the CRP orthologue Vfr (virulence factor regulator) and quorum-sensing regulators LasR and RhlR

Negative regulation of bacterial quorum sensing tunes public goods cooperation

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