scholarly journals Advancing the Quorum in Pseudomonas aeruginosa: MvaT and the Regulation of N-Acylhomoserine Lactone Production and Virulence Gene Expression

2002 ◽  
Vol 184 (10) ◽  
pp. 2576-2586 ◽  
Author(s):  
Stephen P. Diggle ◽  
Klaus Winzer ◽  
Andrée Lazdunski ◽  
Paul Williams ◽  
Miguel Cámara
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Growth Phase ◽  
Virulence Gene ◽  
Homoserine Lactone ◽  
Logarithmic Phase ◽  
Signal Molecules ◽  
Virulence Gene Expression ◽  
Acylhomoserine Lactone

ABSTRACT Pseudomonas aeruginosa regulates the production of many exoproteins and secondary metabolites via a hierarchical quorum-sensing cascade through LasR and RhlR and their cognate signal molecules N-(3-oxododecanoyl)-l-homoserine lactone (3O-C12-HSL) and N-(butanoyl)-l-homoserine lactone (C4-HSL). In this study, we found that transcription of the quorum sensing-regulated genes lecA (coding for PA-IL lectin), lasB (coding for elastase), and rpoS appeared to be growth phase dependent and their expression could not be advanced to the logarithmic phase in cells growing in batch culture by the addition of exogenous C4-HSL and 3O-C12-HSL. To identify novel regulators responsible for this growth phase dependency, a P. aeruginosa lecA::lux reporter strain was subjected to random transposon mutagenesis. A number of mutants affected in lecA expression were found that exhibited altered production of multiple quorum sensing-dependent phenotypes. While some mutations were mapped to new loci such as clpA and mvaT and a putative efflux system, a number of mutations were also mapped to known regulators such as lasR, rhlR, and rpoS. MvaT was identified as a novel global regulator of virulence gene expression, as a mutation in mvaT resulted in enhanced lecA expression and pyocyanin production. This mutant also showed altered swarming ability and production of the LasB and LasA proteases, 3O-C12-HSL, and C4-HSL. Furthermore, addition of exogenous 3O-C12-HSL and C4-HSL to the mvaT mutant significantly advanced lecA expression, suggesting that MvaT is involved in the growth phase-dependent regulation of the lecA gene.

scholarly journals Identification, Timing, and Signal Specificity of Pseudomonas aeruginosa Quorum-Controlled Genes: a Transcriptome Analysis

2003 ◽  
Vol 185 (7) ◽  
pp. 2066-2079 ◽  
Author(s):  
Martin Schuster ◽  
C. Phoebe Lostroh ◽  
Tomoo Ogi ◽  
E. P. Greenberg
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Stationary Phase ◽  
Transcriptome Analysis ◽  
Homoserine Lactone ◽  
Logarithmic Phase ◽  
Acyl Homoserine Lactone ◽  
Global Regulators ◽  
Signaling Systems

ABSTRACT There are two interrelated acyl-homoserine lactone quorum-sensing-signaling systems in Pseudomonas aeruginosa. These systems, the LasR-LasI system and the RhlR-RhlI system, are global regulators of gene expression. We performed a transcriptome analysis to identify quorum-sensing-controlled genes and to better understand quorum-sensing control of P. aeruginosa gene expression. We compared gene expression in a LasI-RhlI signal mutant grown with added signals to gene expression without added signals, and we compared a LasR-RhlR signal receptor mutant to its parent. In all, we identified 315 quorum-induced and 38 quorum-repressed genes, representing about 6% of the P. aeruginosa genome. The quorum-repressed genes were activated in the stationary phase in quorum-sensing mutants but were not activated in the parent strain. The analysis of quorum-induced genes suggests that the signal specificities are on a continuum and that the timing of gene expression is on a continuum (some genes are induced early in growth, most genes are induced at the transition from the logarithmic phase to the stationary phase, and some genes are induced during the stationary phase). In general, timing was not related to signal concentration. We suggest that the level of the signal receptor, LasR, is a critical trigger for quorum-activated gene expression. Acyl-homoserine lactone quorum sensing appears to be a system that allows ordered expression of hundreds of genes during P. aeruginosa growth in culture.

scholarly journals Quorum sensing in bacterial virulence

Microbiology ◽  
2010 ◽  
Vol 156 (8) ◽  
pp. 2271-2282 ◽  
Author(s):  
L. Caetano M. Antunes ◽  
Rosana B. R. Ferreira ◽  
Michelle M. C. Buckner ◽  
B. Brett Finlay
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Target Genes ◽  
Critical Concentration ◽  
Virulence Gene ◽  
Bacterial Virulence ◽  
Signal Molecules ◽  
Control Of Gene Expression ◽  
Virulence Gene Expression

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.

scholarly journals Identification of Synthetic Inducers and Inhibitors of the Quorum-Sensing Regulator LasR in Pseudomonas aeruginosa by High-Throughput Screening

2010 ◽  
Vol 76 (24) ◽  
pp. 8255-8258 ◽  
Author(s):  
Bradley R. Borlee ◽  
Grant D. Geske ◽  
Helen E. Blackwell ◽  
Jo Handelsman
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
High Throughput ◽  
High Throughput Screening ◽  
Virulence Gene ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Virulence Gene Expression ◽  
Significant Interest ◽  
Sensor Strain

ABSTRACT We report the screening of 16,000 synthetic compounds for induction and inhibition of quorum sensing in a Pseudomonas putida N-acylated l-homoserine lactone (AHL) sensor strain engineered with the LasR transcriptional activator. LasR controls virulence gene expression in the opportunistic pathogen Pseudomonas aeruginosa and is of significant interest as a therapeutic target. Nine compounds that inhibit and 14 compounds that induce LasR activity were identified in our high-throughput screen.

scholarly journals Interference with Pseudomonas aeruginosa Quorum Sensing and Virulence by the Mycobacterial Pseudomonas Quinolone Signal Dioxygenase AqdC in Combination with the N-Acylhomoserine Lactone Lactonase QsdA

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Franziska S. Birmes ◽  
Ruth Säring ◽  
Miriam C. Hauke ◽  
Niklas H. Ritzmann ◽  
Steffen L. Drees ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Rhodococcus Erythropolis ◽  
Quorum Quenching ◽  
Signal Molecules ◽  
Content Type ◽  
Acylhomoserine Lactone ◽  
Regulatory Effects ◽  
Epithelial Lung Cells

ABSTRACT The nosocomial pathogen Pseudomonas aeruginosa regulates its virulence via a complex quorum sensing network, which, besides N-acylhomoserine lactones, includes the alkylquinolone signal molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal [PQS]) and 2-heptyl-4(1H)-quinolone (HHQ). Mycobacteroides abscessus subsp. abscessus, an emerging pathogen, is capable of degrading the PQS and also HHQ. Here, we show that although M. abscessus subsp. abscessus reduced PQS levels in coculture with P. aeruginosa PAO1, this did not suffice for quenching the production of the virulence factors pyocyanin, pyoverdine, and rhamnolipids. However, the levels of these virulence factors were reduced in cocultures of P. aeruginosa PAO1 with recombinant M. abscessus subsp. massiliense overexpressing the PQS dioxygenase gene aqdC of M. abscessus subsp. abscessus, corroborating the potential of AqdC as a quorum quenching enzyme. When added extracellularly to P. aeruginosa cultures, AqdC quenched alkylquinolone and pyocyanin production but induced an increase in elastase levels. When supplementing P. aeruginosa cultures with QsdA, an enzyme from Rhodococcus erythropolis which inactivates N-acylhomoserine lactone signals, rhamnolipid and elastase levels were quenched, but HHQ and pyocyanin synthesis was promoted. Thus, single quorum quenching enzymes, targeting individual circuits within a complex quorum sensing network, may also elicit undesirable regulatory effects. Supernatants of P. aeruginosa cultures grown in the presence of AqdC, QsdA, or both enzymes were less cytotoxic to human epithelial lung cells than supernatants of untreated cultures. Furthermore, the combination of both aqdC and qsdA in P. aeruginosa resulted in a decline of Caenorhabditis elegans mortality under P. aeruginosa exposure.

scholarly journals Microarray Analysis of Pseudomonas aeruginosa Quorum-Sensing Regulons: Effects of Growth Phase and Environment

2003 ◽  
Vol 185 (7) ◽  
pp. 2080-2095 ◽  
Author(s):  
Victoria E. Wagner ◽  
Daniel Bushnell ◽  
Luciano Passador ◽  
Andrew I. Brooks ◽  
Barbara H. Iglewski
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Expression Patterns ◽  
Antibiotic Sensitivity ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Medium Composition ◽  
Logarithmic Phase ◽  
Significant Differential Expression ◽  
Biofilm Development

ABSTRACT Bacterial communication via quorum sensing (QS) has been reported to be important in the production of virulence factors, antibiotic sensitivity, and biofilm development. Two QS systems, known as the las and rhl systems, have been identified previously in the opportunistic pathogen Pseudomonas aeruginosa. High-density oligonucleotide microarrays for the P. aeruginosa PAO1 genome were used to investigate global gene expression patterns modulated by QS regulons. In the initial experiments we focused on identifying las and/or rhl QS-regulated genes using a QS signal generation-deficient mutant (PAO-JP2) that was cultured with and without added exogenous autoinducers [N-(3-oxododecanoyl) homoserine lactone and N-butyryl homoserine lactone]. Conservatively, 616 genes showed statistically significant differential expression (P ≤ 0.05) in response to the exogenous autoinducers and were classified as QS regulated. A total of 244 genes were identified as being QS regulated at the mid-logarithmic phase, and 450 genes were identified as being QS regulated at the early stationary phase. Most of the previously reported QS-promoted genes were confirmed, and a large number of additional QS-promoted genes were identified. Importantly, 222 genes were identified as being QS repressed. Environmental factors, such as medium composition and oxygen availability, eliminated detection of transcripts of many genes that were identified as being QS regulated.

scholarly journals Regulation of Quorum Sensing by RpoS inPseudomonas aeruginosa

2000 ◽  
Vol 182 (15) ◽  
pp. 4356-4360 ◽  
Author(s):  
Marvin Whiteley ◽  
Matthew R. Parsek ◽  
E. P. Greenberg
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Gene Transcription ◽  
Opportunistic Pathogen ◽  
Null Mutant ◽  
Global Regulators ◽  
Acylhomoserine Lactone ◽  
Sensing Systems

ABSTRACT The LasR-LasI and RhlR-RhlI quorum-sensing systems are global regulators of gene expression in the opportunistic pathogenPseudomonas aeruginosa. Previous studies suggest that the RhlR-RhlI system activates expression of rpoS. We constructed merodiploid strains of P. aeruginosa containing the native rpoS gene and an rpoS-lacZ fusion. Studies of lacZ transcription in these strains indicated that rpoS was not regulated by RhlR-RhlI. We also generated an rpoS null mutant. This rpoS mutant showed elevated levels of rhlI (but not rhlR) transcription, elevated levels of the RhlI-generated acylhomoserine lactone quorum-sensing signal, and elevated levels of RhlR-RhlI-regulated gene transcription. These findings indicate that there is a relationship between RpoS and quorum sensing, but rather than the RhlR-RhlI system influencing the expression ofrpoS, it appears that RpoS regulates rhlI.

scholarly journals High intracellular c-di-GMP levels antagonize quorum sensing and virulence gene expression in Burkholderia cenocepacia H111

Microbiology ◽  
2017 ◽  
Vol 163 (5) ◽  
pp. 754-764 ◽  
Author(s):  
Nadine Schmid ◽  
Angela Suppiger ◽  
Elisabeth Steiner ◽  
Gabriella Pessi ◽  
Volkhard Kaever ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Virulence Gene ◽  
Burkholderia Cenocepacia ◽  
Virulence Gene Expression

Glucose Decreases Virulence Gene Expression of Escherichia coli O157:H7

2012 ◽  
Vol 75 (4) ◽  
pp. 748-752 ◽  
Author(s):  
V. DELCENSERIE ◽  
G. LaPOINTE ◽  
T. CHARASLERTRANGSI ◽  
A. RABALSKI ◽  
M. W. GRIFFITHS
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Quorum Sensing ◽  
Shiga Toxin ◽  
Virulence Gene ◽  
Escherichia Coli O157 ◽  
Virulence Gene Expression ◽  
E Coli ◽  
Reverse Transcription Pcr ◽  
Enterocyte Effacement

Escherichia coli O157:H7 is responsible for a human toxico-infection that can lead to severe complications such as hemolytic uremic syndrome. Inside the intestine, E. coli O157:H7 forms typical attaching-effacing lesions and produces Shiga toxins. The genes that are responsible for these lesions are located in a pathogenicity island called the locus of enterocyte effacement (LEE). LEE gene expression is influenced by quorum sensing through the luxS system. In this study, the effect of glucose on the expression of several genes from LEE, on the expression of Shiga toxin genes, and on the expression of luxS was assessed with real-time, reverse transcription PCR. All concentrations of glucose (from 0.1 to 1%) were able to down-regulate genes from the LEE operon. A slight down-regulation of genes implicated in Shiga toxin expression was also observed but was significant for low doses of glucose (0.1 to 0.5%) only. A slight but significant increase in luxS expression was observed with 1% glucose. This confirms that in addition to quorum sensing, the presence or absence of nutrients such as glucose has an impact on the down- or upregulation of LEE-encoded virulence genes by the bacterium. The influence of glucose on the virulence of E. coli O157:H7 has received little attention, and these results suggest that glucose can have an important effect on the virulence of E. coli O157:H7.

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