scholarly journals ThePseudomonas aeruginosaOrphan Quorum Sensing Signal Receptor QscR Regulates Global Quorum Sensing Gene Expression by Activating a Single Linked Operon

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Fengming Ding ◽  
Ken-Ichi Oinuma ◽  
Nicole E. Smalley ◽  
Amy L. Schaefer ◽  
Omar Hamwy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Transcription Factor ◽  
Quorum Sensing ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Null Mutant ◽  
Content Type ◽  
Single Operon

ABSTRACTPseudomonas aeruginosauses two acyl-homoserine lactone signals and two quorum sensing (QS) transcription factors, LasR and RhlR, to activate dozens of genes. LasR responds toN-3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and RhlR toN-butanoyl-homoserine lactone (C4-HSL). There is a thirdP. aeruginosaacyl-homoserine-lactone-responsive transcription factor, QscR, which acts to dampen or delay activation of genes by LasR and RhlR by an unknown mechanism. To better understand the role of QscR inP. aeruginosaQS, we performed a chromatin immunoprecipitation analysis, which showed this transcription factor bound the promoter of only a single operon of three genes linked toqscR, PA1895 to PA1897. Other genes that appear to be regulated by QscR in transcriptome studies were not direct targets of QscR. Deletion of PA1897 recapitulates the early QS activation phenotype of a QscR-null mutant, and the phenotype of a QscR-null mutant was complemented by PA1895-1897 but not by PA1897 alone. We conclude that QscR acts to modulate quorum sensing through regulation of a single operon, apparently raising the QS threshold of the population and providing a “brake” on QS autoinduction.IMPORTANCEQuorum sensing, a cell-cell communication system, is broadly distributed among bacteria and is commonly used to regulate the production of shared products. An important consequence of quorum sensing is a delay in production of certain products until the population density is high. The bacteriumPseudomonas aeruginosahas a particularly complicated quorum sensing system involving multiple signals and receptors. One of these receptors, QscR, downregulates gene expression, unlike the other receptors inP. aeruginosa. QscR does so by inducing the expression of a single operon whose function provides an element of resistance to a population reaching a quorum. This finding has importance for design of quorum sensing inhibitory strategies and can also inform design of synthetic biological circuits that use quorum sensing receptors to regulate gene expression.

scholarly journals PqsE Is Essential for RhlR-Dependent Quorum Sensing Regulation in Pseudomonas aeruginosa

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Marie-Christine Groleau ◽  
Thays de Oliveira Pereira ◽  
Valérie Dekimpe ◽  
Eric Déziel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Cell Communication ◽  
Transcriptional Regulator ◽  
Homoserine Lactone ◽  
World Health ◽  
Chronic Infections ◽  
Content Type ◽  
Main Regulator ◽  
Health Organization

ABSTRACT The bacterium Pseudomonas aeruginosa has emerged as a central threat in health care settings and can cause a large variety of infections. It expresses an arsenal of virulence factors and a diversity of survival functions, many of which are finely and tightly regulated by an intricate circuitry of three quorum sensing (QS) systems. The las system is considered at the top of the QS hierarchy and activates the rhl and pqs systems. It is composed of the LasR transcriptional regulator and the LasI autoinducer synthase, which produces 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), the ligand of LasR. RhlR is the transcriptional regulator for the rhl system and is associated with RhlI, which produces its cognate autoinducer C4-HSL. The third QS system is composed of the pqsABCDE operon and the MvfR (PqsR) regulator. PqsABCD synthetize 4-hydroxy-2-alkylquinolines (HAQs), which include ligands activating MvfR. PqsE is not required for HAQ production and instead is associated with the expression of genes controlled by the rhl system. While RhlR is often considered the main regulator of rhlI, we confirmed that LasR is in fact the principal regulator of C4-HSL production and that RhlR regulates rhlI and production of C4-HSL essentially only in the absence of LasR by using liquid chromatography-mass spectrometry quantifications and gene expression reporters. Investigating the expression of RhlR targets also clarified that activation of RhlR-dependent QS relies on PqsE, especially when LasR is not functional. This work positions RhlR as the key QS regulator and points to PqsE as an essential effector for full activation of this regulation. IMPORTANCE Pseudomonas aeruginosa is a versatile bacterium found in various environments. It can cause severe infections in immunocompromised patients and naturally resists many antibiotics. The World Health Organization listed it among the top priority pathogens for research and development of new antimicrobial compounds. Quorum sensing (QS) is a cell-cell communication mechanism, which is important for P. aeruginosa adaptation and pathogenesis. Here, we validate the central role of the PqsE protein in QS particularly by its impact on the regulator RhlR. This study challenges the traditional dogmas of QS regulation in P. aeruginosa and ties loose ends in our understanding of the traditional QS circuit by confirming RhlR to be the main QS regulator in P. aeruginosa. PqsE could represent an ideal target for the development of new control methods against the virulence of P. aeruginosa. This is especially important when considering that LasR-defective mutants frequently arise, e.g., in chronic infections.

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 Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection

2012 ◽  
Vol 57 (1) ◽  
pp. 569-578 ◽  
Author(s):  
Moayad Alhariri ◽  
Abdelwahab Omri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Homoserine Lactone ◽  
Protease Production ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Signal Molecule ◽  
Intratracheal Administration ◽  
Content Type

ABSTRACTWe sought to investigate alterations in quorum-sensing signal moleculeN-acyl homoserine lactone secretion and in the release ofPseudomonas aeruginosavirulence factors, as well as thein vivoantimicrobial activity of bismuth-ethanedithiol incorporated into a liposome-loaded tobramycin formulation (LipoBiEDT-TOB) administered to rats chronically infected withP. aeruginosa. The quorum-sensing signal moleculeN-acyl homoserine lactone was monitored by using a biosensor organism.P. aeruginosavirulence factors were assessed spectrophotometrically. An agar beads model of chronicPseudomonaslung infection in rats was used to evaluate the efficacy of the liposomal formulation in the reduction of bacterial count. The levels of active tobramycin in the lungs and the kidneys were evaluated by microbiological assay. LipoBiEDT-TOB was effective in disrupting both quorum-sensing signal moleculesN-3-oxo-dodeccanoylhomoserine lactone andN-butanoylhomoserine lactone, as well as significantly (P< 0.05) reducing lipase, chitinase, and protease production. At 24 h after 3 treatments, the CFU counts in lungs of animals treated with LipoBiEDT-TOB were of 3 log10CFU/lung, comparated to 7.4 and 4.7 log10CFU/lung, respectively, in untreated lungs and in lungs treated with free antibiotic. The antibiotic concentration after the last dose of LipoBiEDT-TOB was 25.1 μg/lung, while no tobramycin was detected in the kidneys. As for the free antibiotic, we found 6.5 μg/kidney but could not detect any tobramycin in the lungs. Taken together, LipoBiEDT-TOB reduced the production of quorum-sensing molecules and virulence factors and could highly improve the management of chronic pulmonary infection in cystic fibrosis patients.

scholarly journals Novel Pseudomonas aeruginosa Quorum-Sensing Inhibitors Identified in an Ultra-High-Throughput Screen

2006 ◽  
Vol 50 (11) ◽  
pp. 3674-3679 ◽  
Author(s):  
Ute Müh ◽  
Martin Schuster ◽  
Roger Heim ◽  
Ashvani Singh ◽  
Eric R. Olson ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Transcription Factor ◽  
Quorum Sensing ◽  
High Throughput ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Virulence Determinants ◽  
Chemical Structures ◽  
Alkyl Tail

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa has two complete acyl-homoserine lactone (acyl-HSL) signaling systems, LasR-LasI and RhlR-RhlI. LasI catalyzes the synthesis of N-3-oxododecanoyl homoserine lactone (3OC12-HSL), and LasR is a transcription factor that requires 3OC12-HSL as a ligand. RhlI catalyzes the synthesis of N-butanoyl homoserine lactone (C4), and RhlR is a transcription factor that responds to C4. LasR and RhlR control the transcription of hundreds of P. aeruginosa genes, many of which are critical virulence determinants, and LasR is required for RhlR function. We developed an ultra-high-throughput cell-based assay to screen a library of approximately 200,000 compounds for inhibitors of LasR-dependent gene expression. Although the library contained a large variety of chemical structures, the two best inhibitors resembled the acyl-homoserine lactone molecule that normally binds to LasR. One compound, a tetrazole with a 12-carbon alkyl tail designated PD12, had a 50% inhibitory concentration (IC50) of 30 nM. The second compound, V-06-018, had an IC50 of 10 μM and is a phenyl ring with a 12-carbon alkyl tail. A microarray analysis showed that both compounds were general inhibitors of quorum sensing, i.e., the expression levels of most LasR-dependent genes were affected. Both compounds also inhibited the production of two quorum-sensing-dependent virulence factors, elastase and pyocyanin. These compounds should be useful for studies of LasR-dependent gene regulation and might serve as scaffolds for the identification of new quorum-sensing modulators.

scholarly journals Quorum sensing differentially regulates Pseudomonas aeruginosa type VI secretion locus I and homologous loci II and III, which are required for pathogenesis

Microbiology ◽  
2009 ◽  
Vol 155 (9) ◽  
pp. 2845-2855 ◽  
Author(s):  
B. Lesic ◽  
M. Starkey ◽  
J. He ◽  
R. Hazan ◽  
L. G. Rahme
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Gene Regulation ◽  
Transcription Factor ◽  
Quorum Sensing ◽  
Transcriptional Regulator ◽  
Homoserine Lactone ◽  
Plant Infection ◽  
Type Vi Secretion ◽  
Expression Of Genes

Pseudomonas aeruginosa harbours three type VI secretion (T6S) loci. Although HSI-I has been partially studied, limited knowledge is available on the homologous loci HSI-II and HSI-III. We show that quorum sensing (QS) differentially regulates the expression of genes at all three loci. HSI-I-associated gene expression is suppressed by both the homoserine lactone transcription factor LasR and the 4-hydroxy-2-alkylquinoline (HAQ) transcriptional regulator MvfR. Conversely, both HSI-II and HSI-III loci are positively controlled by LasR and MvfR. PqsE, a key component of the MvfR regulon, is required for the expression of part of HSI-III but not HSI-II, and previously identified inhibitors of HAQ biosynthesis significantly downregulate HSI-II and -III gene expression. Animal and plant infection studies reveal that both HSI-II and -III play important roles in pathogenesis. Furthermore, analysis of a double ΔHSI-II : : III mutant suggests that these loci functionally compensate for one another in virulence. This study illustrates the contribution of the QS systems to T6S gene regulation and reveals the importance of HSI-II and -III in mediating P. aeruginosa pathogenesis. Moreover, this work provides new insights into the design and development of selective compounds that may restrict human P. aeruginosa and possibly other clinical infections.

Biofilm Formation, Communication and Interactions of Mesophilic Leaching Bacteria during Pyrite Oxidation

2013 ◽  
Vol 825 ◽  
pp. 107-110
Author(s):  
Sören Bellenberg ◽  
Robert Barthen ◽  
Mario Vera ◽  
Nicolas Guiliani ◽  
Wolfgang Sand
Keyword(s):  
Quorum Sensing ◽  
Acidithiobacillus Ferrooxidans ◽  
Biofilm Formation ◽  
Pyrite Oxidation ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Mixed Cultures ◽  
Acyl Homoserine Lactone ◽  
Leaching Bacteria ◽  
Leaching Efficiency

A functional luxIR-type Quorum Sensing (QS) system is present in Acidithiobacillus ferrooxidans. However, cell-cell communication among various acidophilic chemolithoautotrophs growing on pyrite has not been studied in detail. These aspects are the scope of this study with emphasis on the effects exerted by the N-acyl-homoserine lactone (AHL) type signaling molecules which are produced by Acidithiobacillus ferrooxidans. Their effects on attachment and leaching efficiency by other leaching bacteria, such as Acidithiobacillus ferrivorans, Acidiferrobacter spp. SPIII/3 and Leptospirillum ferrooxidans in pure and mixed cultures growing on pyrite is shown.

scholarly journals LuxR- and LuxI-Type Quorum-Sensing Circuits Are Prevalent in Members of the Populus deltoides Microbiome

2013 ◽  
Vol 79 (18) ◽  
pp. 5745-5752 ◽  
Author(s):  
Amy L. Schaefer ◽  
Colin R. Lappala ◽  
Ryan P. Morlen ◽  
Dale A. Pelletier ◽  
Tse-Yuan S. Lu ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Populus Deltoides ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Bacterial Isolates ◽  
Content Type ◽  
Eastern Cottonwood ◽  
Bacterial Signaling ◽  
Signal Production ◽  
Plant Signals

ABSTRACTWe are interested in the root microbiome of the fast-growing Eastern cottonwood tree,Populus deltoides. There is a large bank of bacterial isolates fromP. deltoides, and there are 44 draft genomes of bacterial endophyte and rhizosphere isolates. As a first step in efforts to understand the roles of bacterial communication and plant-bacterial signaling inP. deltoides, we focused on the prevalence of acyl-homoserine lactone (AHL) quorum-sensing-signal production and reception in members of theP. deltoidesmicrobiome. We screened 129 bacterial isolates for AHL production using a broad-spectrum bioassay that responds to many but not all AHLs, and we queried the available genome sequences of microbiome isolates for homologs of AHL synthase and receptor genes. AHL signal production was detected in 40% of 129 strains tested. Positive isolates included members of theAlpha-,Beta-, andGammaproteobacteria. Members of theluxIfamily of AHL synthases were identified in 18 of 39 proteobacterial genomes, including genomes of some isolates that tested negative in the bioassay. Members of theluxRfamily of transcription factors, which includes AHL-responsive factors, were more abundant thanluxIhomologs. There were 72 in the 39 proteobacterial genomes. Some of theluxRhomologs appear to be members of a subfamily of LuxRs that respond to as-yet-unknown plant signals rather than bacterial AHLs. Apparently, there is a substantial capacity for AHL cell-to-cell communication in proteobacteria of theP. deltoidesmicrobiota, and there are alsoProteobacteriawith LuxR homologs of the type hypothesized to respond to plant signals or cues.

scholarly journals Disruption of Quorum Sensing and Virulence inBurkholderia cenocepaciaby a Structural Analogue of thecis-2-Dodecenoic Acid Signal

2019 ◽  
Vol 85 (8) ◽  
Author(s):  
Chaoyu Cui ◽  
Shihao Song ◽  
Chunxi Yang ◽  
Xiuyun Sun ◽  
Yutong Huang ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Burkholderia Cenocepacia ◽  
Enoic Acid ◽  
Acyl Homoserine Lactone ◽  
Structural Analogue ◽  
Content Type ◽  
Signal Production

ABSTRACTQuorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities.Burkholderia cenocepaciaemploys a molecular mechanism in which thecis-2-dodecenoic acid (namedBurkholderiadiffusiblesignalfactor [BDSF]) QS system regulatesN-acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling inB. cenocepacia. A novel structural analogue of BDSF, 14-Me-C16:Δ2(cis-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes inB. cenocepacia, including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C16:Δ2also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C16:Δ2inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C16:Δ2attenuated BDSF-regulated phenotypes in variousBurkholderiaspecies. These findings suggest that 14-Me-C16:Δ2could potentially be developed as a new therapeutic agent against pathogenicBurkholderiaspecies by interfering with their QS signaling.IMPORTANCEBurkholderia cenocepaciais an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including thecis-2-dodecenoic acid (BDSF) system andN-acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (cis-14-methylpentadec-2-enoic acid [14-Me-C16:Δ2]) that is capable of interfering withB. cenocepaciaQS signaling and virulence. We demonstrate that 14-Me-C16:Δ2reduced BDSF and AHL signal production inB. cenocepacia. It also impaired QS-regulated phenotypes in variousBurkholderiaspecies. These results suggest that 14-Me-C16:Δ2could interfere with QS signaling in manyBurkholderiaspecies and might be developed as a new antibacterial agent.

scholarly journals Alginate Oligosaccharide-Induced Modification of the lasI-lasR and rhlI-rhlR Quorum-Sensing Systems in Pseudomonas aeruginosa

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Alison A. Jack ◽  
Saira Khan ◽  
Lydia C. Powell ◽  
Manon F. Pritchard ◽  
Konrad Beck ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Laser Scanning ◽  
Homoserine Lactone ◽  
Laser Scanning Microscopy ◽  
Extracellular Dna ◽  
Mass Spectrometry Analysis ◽  
Confocal Laser ◽  
Steric Interaction ◽  
Content Type

ABSTRACT Pseudomonas aeruginosa plays a major role in many chronic infections. Its ability to readily form biofilms contributes to its success as an opportunistic pathogen and its resistance/tolerance to antimicrobial/antibiotic therapy. A low-molecular-weight alginate oligomer (OligoG CF-5/20) derived from marine algae has previously been shown to impair motility in P. aeruginosa biofilms and disrupt pseudomonal biofilm assembly. As these bacterial phenotypes are regulated by quorum sensing (QS), we hypothesized that OligoG CF-5/20 may induce alterations in QS signaling in P. aeruginosa . QS regulation was studied by using Chromobacterium violaceum CV026 biosensor assays that showed a significant reduction in acyl homoserine lactone (AHL) production following OligoG CF-5/20 treatment (≥2%; P < 0.05). This effect was confirmed by liquid chromatography-mass spectrometry analysis of C 4 -AHL and 3-oxo-C 12 -AHL production (≥2%; P < 0.05). Moreover, quantitative PCR showed that reduced expression of both the las and rhl systems was induced following 24 h of treatment with OligoG CF-5/20 (≥0.2%; P < 0.05). Circular dichroism spectroscopy indicated that these alterations were not due to steric interaction between the AHL and OligoG CF-5/20. Confocal laser scanning microscopy (CLSM) and COMSTAT image analysis demonstrated that OligoG CF-5/20-treated biofilms had a dose-dependent decrease in biomass that was associated with inhibition of extracellular DNA synthesis (≥0.5%; P < 0.05). These changes correlated with alterations in the extracellular production of the pseudomonal virulence factors pyocyanin, rhamnolipids, elastase, and total protease ( P < 0.05). The ability of OligoG CF-5/20 to modify QS signaling in P. aeruginosa PAO1 may influence critical downstream functions such as virulence factor production and biofilm formation.

Sign in / Sign up

Export Citation Format

Share Document