A bacterial cell to cell signal in the lungs of cystic fibrosis patients

Collier, David N.; Anderson, Lisa; McKnight, Susan L.; Noah, Terry L.; Knowles, Michael R.; Boucher, Richard C.; Schwab, Ute; Gilligan, Peter H.; Pesci, Everett C.

doi:10.1111/j.1574-6968.2002.tb11367.x

Cited by 179 publications

(163 citation statements)

References 24 publications

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“…Nonetheless, there is considerable evidence in the literature supporting our view that acyl-HSL control of P. aeruginosa metabolism is relevant in conditions extant in the pathogenic environment of the cystic fibrosis (CF) lung. Previous studies documenting the presence of PQS in CF sputum imply the availability of anthranilate, a PQS precursor (34,35). Together with previously reported findings, our results demonstrate that the PQS biosynthesis pathway and the anthranilate degradation pathway for energy metabolism draw from the same pool of intracellular anthranilate (27).…”

Section: C10-hsl-dependent Induction Of Catb Relies On Anthranilate Psupporting

confidence: 81%

LuxR homolog-independent gene regulation by acyl-homoserine lactones in Pseudomonas aeruginosa

Chugani

Greenberg

2010

Proc. Natl. Acad. Sci. U.S.A.

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Pseudomonas aeruginosa quorum control of gene expression involves three LuxR-type signal receptors LasR, RhlR, and QscR that respond to the LasI-and RhlI-generated acyl-homoserine lactone (acyl-HSL) signals 3OC12-HSL and C4-HSL. We found that a LasRRhlR-QscR triple mutant responds to acyl-HSLs by regulating at least 37 genes. LuxR homolog-independent activation of the representative genes antA and catB also occurs in the wild type. Expression of antA was influenced the most by C10-HSL and to a lesser extent by other acyl-HSLs, including the P. aeruginosa 3OC12-HSL and C4-HSL signals. The ant and cat operons encode enzymes for the degradation of anthranilate to tricarboxylic acid cycle intermediates. Our results indicate that LuxR homologindependent acyl-HSL control of the ant and cat operons occurs via regulation of antR, which codes for the transcriptional activator of the ant operon. Although P. aeruginosa has multiple pathways for anthranilate synthesis, one pathway-the kynurenine pathway for tryptophan degradation-is required for acyl-HSL activation of the ant operon. The kynurenine pathway is also the critical source of anthranilate for energy metabolism via the antABC gene products, as well as the source of anthranilate for synthesis of the P. aeruginosa quinolone signal. Our discovery of LuxR homolog-independent responses to acyl-HSLs provides insight into acyl-HSL signaling.anthranilate | gene regulation | quorum sensing T he metabolically versatile bacterium Pseudomonas aeruginosa is ubiquitous and can adapt to diverse habitats. For example, it can be found in soil and water or as an opportunistic pathogen in a wide range of hosts, including plants and humans. The expression of a large number of P. aeruginosa genes, including virulence genes, is controlled by a signaling mechanism called quorum sensing. Quorum sensing involves production and sensing of chemical signals that allow bacteria to regulate gene expression in response to alterations in cell density (1-4). The archetypical LuxI-R quorum-sensing system that controls luminescence in Vibrio fischeri uses the enzyme LuxI to generate a diffusible acyl-homoserine lactone (acyl-HSL) signal, 3-oxohexanoyl-HSL, which binds to the acyl-HSL receptor and transcription factor LuxR (5, 6). Similar quorum-sensing systems have been found in about 100 species of Proteobacteria, where they function as regulators of a range of functions. Acyl-HSL quorum sensing commonly controls extracellular products, such as exoproteases, exopolysaccharides, antibiotics, and aggregation factors (7-10).P. aeruginosa has two acyl-HSL synthases and three receptors (11)(12)(13)(14). The LasI synthase produces 3-oxo-C12-HSL, for which there are two receptors, LasR and QscR. The RhlI synthase produces C4-HSL, for which the receptor is RhlR. Together these quorum-sensing systems regulate hundreds of P. aeruginosa genes. Different elements of the P. aeruginosa quorum sensing circuit also influence each other at multiple levels; for example, LasR-3OC12-HSL activates rhlR and rhlI transc...

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Section: C10-hsl-dependent Induction Of Catb Relies On Anthranilate Psupporting

confidence: 81%

LuxR homolog-independent gene regulation by acyl-homoserine lactones in Pseudomonas aeruginosa

Chugani

Greenberg

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…4 shows that the rsmA mutant produced less PQS than PAO1 wild-type in stationary phase and that PAO1 overexpressing rsmA produced more PQS than PAO1 wild-type. This was accompanied by a parallel reduction in the intensity of the upper band, namely compound B; this compound has not yet been identified, but its levels have been found to parallel PQS levels in certain P. aeruginosa strains, including PAO1 (Collier et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

Influence of the regulatory protein RsmA on cellular functions in Pseudomonas aeruginosa PAO1, as revealed by transcriptome analysis

et al. 2006

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RsmA is a posttranscriptional regulatory protein in Pseudomonas aeruginosa that works in tandem with a small non-coding regulatory RNA molecule, RsmB (RsmZ), to regulate the expression of several virulence-related genes, including the N-acyl-homoserine lactone synthase genes lasI and rhlI, and the hydrogen cyanide and rhamnolipid biosynthetic operons. Although these targets of direct RsmA regulation have been identified, the full impact of RsmA on cellular activities is not as yet understood. To address this issue the transcriptome profiles of P. aeruginosa PAO1 and an isogenic rsmA mutant were compared. Loss of RsmA altered the expression of genes involved in a variety of pathways and systems important for virulence, including iron acquisition, biosynthesis of the Pseudomonas quinolone signal (PQS), the formation of multidrug efflux pumps, and motility. Not all of these effects can be explained through the established regulatory roles of RsmA. This study thus provides both a first step towards the identification of further genes under RsmA posttranscriptional control in P. aeruginosa and a fuller understanding of the broader impact of RsmA on cellular functions.

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“…PQS has been shown to affect biofilm formation and to regulate several virulence factors in P. aeruginosa, including elastase, pyocyanin and LecA lectin, and it is considered essential for full virulence in multiple hosts (Cao et al, 2001;Rahme et al, 1997Rahme et al, , 2000. PQS has been found in sputum, bronchoalveolar fluid and mucopurulent fluid from CF patients, suggesting that it may play an important role during the infection process (Collier et al, 2002). Besides controlling bacterial virulence, PQS and HHQ have been shown to downregulate the host immune response through NFkB (Kim et al, 2009b).…”

Section: C M Antunes and Othersmentioning

confidence: 99%

Quorum sensing in bacterial virulence

et al. 2010

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Bacteria communicate through the production of diffusible signal molecules termed autoinducers. The molecules are produced at basal levels and accumulate during growth. Once a critical concentration has been reached, autoinducers can activate or repress a number of target genes. Because the control of gene expression by autoinducers is cell-density-dependent, this phenomenon has been called quorum sensing. Quorum sensing controls virulence gene expression in numerous micro-organisms. In some cases, this phenomenon has proven relevant for bacterial virulence in vivo. In this article, we provide a few examples to illustrate how quorum sensing can act to control bacterial virulence in a multitude of ways. Several classes of autoinducers have been described to date and we present examples of how each of the major types of autoinducer can be involved in bacterial virulence. As quorum sensing controls virulence, it has been considered an attractive target for the development of new therapeutic strategies. We discuss some of the new strategies to combat bacterial virulence based on the inhibition of bacterial quorum sensing systems.

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A bacterial cell to cell signal in the lungs of cystic fibrosis patients

Cited by 179 publications

References 24 publications

LuxR homolog-independent gene regulation by acyl-homoserine lactones in Pseudomonas aeruginosa

LuxR homolog-independent gene regulation by acyl-homoserine lactones in Pseudomonas aeruginosa

Influence of the regulatory protein RsmA on cellular functions in Pseudomonas aeruginosa PAO1, as revealed by transcriptome analysis

Quorum sensing in bacterial virulence

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