P. aeruginosa quorum-sensing systems and virulence

Smith, Roger S.

doi:10.1016/s1369-5274(03)00008-0

Cited by 620 publications

(471 citation statements)

References 42 publications

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“…Quorum sensing regulates the production of several extracellular virulence factors, promotes biofilm maturation and regulates the expression of antibiotic efflux pumps, meaning that it has a key role in the pathogenesis of P. aeruginosa (Dekimpe & Déziel, 2009;Diggle et al, 2006;Fuqua et al, 2001;Schuster & Greenberg, 2006;Swift et al, 2001;Wagner et al, 2003;Whitehead et al, 2001). The las and rhl systems regulate the timing and production of multiple virulence factors, including elastase, alkaline protease, exotoxin A, rhamnolipids, pyocyanin, lectins and superoxidase dismutase (Schuster et al, 2003;Smith & Iglewski, 2003). The expression of these two quorum sensing systems has also been linked to the regulation of biofilm formation.…”

Section: Quorum Sensing In Staphylococcus Aureus Virulencementioning

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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Section: Quorum Sensing In Staphylococcus Aureus Virulencementioning

confidence: 99%

Quorum sensing in bacterial virulence

et al. 2010

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“…This Gram-negative bacterium produces and responds to diffusible intercellular signals and autoinducers that mediate pathogenicity via the coordinated expression of a large array of virulence genes (Rumbaugh et al, 2000;Smith & Iglewski, 2003). This cell-density-dependent regulation is termed quorum sensing (QS) (Fuqua et al, 2001), as autoinducer concentrations increase, up to a threshold, with increasing cell density.…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry

2006

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The LysR-type transcriptional regulator MvfR (PqsR) (multiple virulence factor regulator) plays a critical role in Pseudomonas aeruginosa pathogenicity via the transcriptional regulation of multiple quorum-sensing (QS)-regulated virulence factors. LasR activates full mvfR transcription, and MvfR subsequently activates pqsA-E expression. This study identifies and characterizes the key cis-regulatory elements through which mvfR and pqsA-E transcription is regulated in the highly virulent P. aeruginosa strain PA14. Deletion and site-directed mutagenesis indicate that: (1) LasR activates mvfR transcription by binding to a las/rhl box, CTAACAAAAGACATAG, centred at "513 bp upstream of the MvfR translational start site; and (2) RhlR represses pqsA transcription by binding to a las/rhl box, CTGTGAGATTTGGGAG, centred at "311 bp upstream of the pqsA transcriptional initiation site. Furthermore, it is shown that MvfR activates pqsA-E transcription by binding to a LysR box, TTCGGACTCCGAA, centred at "45 bp relative to the pqsA transcriptional initiation site, demonstrating that this LysR box has a critical role in the physical interaction between the MvfR protein and the pqsA promoter. These results provide new insights into the regulatory relationships between LasR and mvfR, and between MvfR/RhlR and the pqs operon, and elucidate further the complex regulation of the P. aeruginosa QS circuitry.

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“…In P. aeruginosa, the formation of numerous virulence factors is controlled to a large extent by a mechanism called quorum sensing (QS) (Fuqua & Greenberg, 1998;Wagner et al, 2003;Schuster et al, 2003;Hentzer et al, 2003;Juhas et al, 2004). Two host defences in a cell-density-dependent manner (Smith & Iglewski, 2003). There is, however, increasing evidence to suggest that the cell-to-cell signalling mediated by the QS system can also be strongly affected by environmental factors other than the cell density.…”

Section: Introductionmentioning

confidence: 99%

Expression of the quorum-sensing regulatory protein LasR is strongly affected by iron and oxygen concentrations in cultures of Pseudomonas aeruginosa irrespective of cell density

et al. 2005

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Expression of the quorum-sensing regulatory protein LasR is strongly affected by iron and oxygen concentrations in cultures of Pseudomonas aeruginosa irrespective of cell density The expression of the transcriptional regulatory protein LasR, a main component of the quorum-sensing (QS) system in Pseudomonas aeruginosa, was recently found to be sensitive to several environmental factors in addition to its dependency on cell density. However, the inherent effects of the different factors have seldom been separately demonstrated due to concurrent changes of culture conditions in typical experimental settings. Furthermore, the interplays of the different factors are unknown. In this work, the effects and interplay of iron concentration and dissolved oxygen tension (pO 2 ) on the expression of lasR in P. aeruginosa were studied in defined growth media with varied iron concentration and pO 2 values in computer-controlled batch and continuous cultures. b-Galactosidase activity in a recombinant P. aeruginosa PAO1 (NCCB 2452) strain with a lasRp-lacZ fusion was used as a reporter for lasR expression. In batch culture with a constant pO 2 <10 % air saturation, a strong correlation between the exhaustion of iron and the increase of lasR expression was observed. In continuous culture with nearly constant cell density but varied pO 2 values, lasR expression generally increased with increasing oxidative stress with the exception of growth under O 2 -limited conditions (pO 2 <0 %). Under O 2 limitation, the expression of lasR strongly depended on the concentration of iron. It showed a nearly twofold increase in cells grown under iron deprivation in comparison with cells grown in iron-replete conditions and reached the expression level seen at high oxidative stress. A preliminary proteomic analysis was carried out for extracellular proteins in samples from batch cultures grown under different iron concentrations. Several of the extracellular proteins (e.g. AprA, LasB, PrpL) which were up-regulated under iron-limited conditions were found to be QS regulated proteins. Thus, this study clearly shows the links between QS and genes involved in iron and oxygen regulation in P. aeruginosa. INTRODUCTIONPseudomonas aeruginosa, a Gram-negative opportunistic human pathogen, is often found in nosocomial infections. In particular, it can cause chronic pulmonary infection of cystic fibrosis patients, leading to a high mortality rate due to the formation of virulence factors and the inappropriate host response (Hybiske et al., 2004;Wolfgang et al., 2004;Lyczak et al., 2002). In P. aeruginosa, the formation of numerous virulence factors is controlled to a large extent by a mechanism called quorum sensing (QS) (Fuqua & Greenberg, 1998;Wagner et al., 2003;Schuster et al., 2003;Hentzer et al., 2003;Juhas et al., 2004). Two major genetic components of QS, the las and rhl systems, have been identified in P. aeruginosa. The las system consists of LasR, a transcriptional regulatory protein, and LasI, the autoinducer synthase that controls the producti...

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P. aeruginosa quorum-sensing systems and virulence

Cited by 620 publications

References 42 publications

Quorum sensing in bacterial virulence

Quorum sensing in bacterial virulence

Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry

Expression of the quorum-sensing regulatory protein LasR is strongly affected by iron and oxygen concentrations in cultures of Pseudomonas aeruginosa irrespective of cell density

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