scholarly journals The flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1

Microbiology ◽  
2011 ◽  
Vol 157 (7) ◽  
pp. 2120-2132 ◽  
Author(s):  
Olivier M. Vandeputte ◽  
Martin Kiendrebeogo ◽  
Tsiry Rasamiravaka ◽  
Caroline Stévigny ◽  
Pierre Duez ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Gene Products ◽  
Strain Pao1 ◽  
Preliminary Screening ◽  
Mutant Strains

Preliminary screening of the Malagasy plant Combretum albiflorum for compounds attenuating the production of quorum sensing (QS)-controlled virulence factors in bacteria led to the identification of active fractions containing flavonoids. In the present study, several flavonoids belonging to the flavone, flavanone, flavonol and chalcone structural groups were screened for their capacity to reduce the production of QS-controlled factors in the opportunistic pathogen Pseudomonas aeruginosa (strain PAO1). Flavanones (i.e. naringenin, eriodictyol and taxifolin) significantly reduced the production of pyocyanin and elastase in P. aeruginosa without affecting bacterial growth. Consistently, naringenin and taxifolin reduced the expression of several QS-controlled genes (i.e. lasI, lasR, rhlI, rhlR, lasA, lasB, phzA1 and rhlA) in P. aeruginosa PAO1. Naringenin also dramatically reduced the production of the acylhomoserine lactones N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL), which is driven by the lasI and rhlI gene products, respectively. In addition, using mutant strains deficient for autoinduction (ΔlasI and ΔrhlI) and LasR- and RhlR-based biosensors, it was shown that QS inhibition by naringenin not only is the consequence of a reduced production of autoinduction compounds but also results from a defect in the proper functioning of the RlhR–C4-HSL complex. Widely distributed in the plant kingdom, flavonoids are known for their numerous and determinant roles in plant physiology, plant development and in the success of plant–rhizobia interactions, but, as shown here, some of them also have a role as inhibitors of the virulence of pathogenic bacteria by interfering with QS mechanisms.

scholarly journals Identification of Catechin as One of the Flavonoids from Combretum albiflorum Bark Extract That Reduces the Production of Quorum-Sensing-Controlled Virulence Factors in Pseudomonas aeruginosa PAO1

2009 ◽  
Vol 76 (1) ◽  
pp. 243-253 ◽  
Author(s):  
Olivier M. Vandeputte ◽  
Martin Kiendrebeogo ◽  
Sanda Rajaonson ◽  
Billo Diallo ◽  
Adeline Mol ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Higher Plants ◽  
Homoserine Lactone ◽  
Bark Extract ◽  
Negative Effect ◽  
Virulence Factor Production

ABSTRACT Quorum-sensing (QS) regulates the production of key virulence factors in Pseudomonas aeruginosa and other important pathogenic bacteria. In this report, extracts of leaves and bark of Combretum albiflorum (Tul.) Jongkind (Combretaceae) were found to quench the production of QS-dependent factors in P. aeruginosa PAO1. Chromatographic fractionation of the crude active extract generated several active fractions containing flavonoids, as shown by their typical spectral features. Purification and structural characterization of one of the active compounds led to the identification of the flavan-3-ol catechin [(2R,3S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol]. The identity of catechin as one of the active molecules was confirmed by comparing the high-pressure liquid chromatography profiles and the mass spectrometry spectra obtained for a catechin standard and for the active C. albiflorum fraction. Moreover, standard catechin had a significant negative effect on pyocyanin and elastase productions and biofilm formation, as well as on the expression of the QS-regulated genes lasB and rhlA and of the key QS regulatory genes lasI, lasR, rhlI, and rhlR. The use of RhlR- and LasR-based biosensors indicated that catechin might interfere with the perception of the QS signal N-butanoyl-l-homoserine lactone by RhlR, thereby leading to a reduction of the production of QS factors. Hence, catechin, along with other flavonoids produced by higher plants, might constitute a first line of defense against pathogenic attacks by affecting QS mechanisms and thereby virulence factor production.

scholarly journals Regulation of Pseudomonas Quinolone Signal Synthesis in Pseudomonas aeruginosa

2005 ◽  
Vol 187 (13) ◽  
pp. 4372-4380 ◽  
Author(s):  
Dana S. Wade ◽  
M. Worth Calfee ◽  
Edson R. Rocha ◽  
Elizabeth A. Ling ◽  
Elana Engstrom ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Transcriptional Start Site ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Mobility Shift ◽  
Sensing System ◽  
Regulator Protein ◽  
Quorum Sensing System

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in cystic fibrosis patients and is a major source of nosocomial infections. This bacterium controls many virulence factors by using two quorum-sensing systems, las and rhl. The las system is composed of the LasR regulator protein and its cell-to-cell signal, N-(3-oxododecanoyl) homoserine lactone, and the rhl system is composed of RhlR and the signal N-butyryl homoserine lactone. A third intercellular signal, the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone), also regulates numerous virulence factors. PQS synthesis requires the expression of multiple operons, one of which is pqsABCDE. Previous experiments showed that the transcription of this operon, and therefore PQS production, is negatively regulated by the rhl quorum-sensing system and positively regulated by the las quorum-sensing system and PqsR (also known as MvfR), a LysR-type transcriptional regulator protein. With the use of DNA mobility shift assays and β-galactosidase reporter fusions, we have studied the regulation of pqsR and its relationship to pqsA, lasR, and rhlR. We show that PqsR binds the promoter of pqsA and that this binding increases dramatically in the presence of PQS, implying that PQS acts as a coinducer for PqsR. We have also mapped the transcriptional start site for pqsR and found that the transcription of pqsR is positively regulated by lasR and negatively regulated by rhlR. These results suggest that a regulatory chain occurs where pqsR is under the control of LasR and RhlR and where PqsR in turn controls pqsABCDE, which is required for the production of PQS.

scholarly journals Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors

Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 712-723 ◽  
Author(s):  
Valérie Dekimpe ◽  
Eric Déziel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Transcriptional Regulator ◽  
Homoserine Lactone ◽  
The Other ◽  
Virulence Determinants ◽  
Late Stationary Phase ◽  
Regulatory Systems ◽  
Specific Factors

Pseudomonas aeruginosa uses the two major quorum-sensing (QS) regulatory systems las and rhl to modulate the expression of many of its virulence factors. The las system is considered to stand at the top of the QS hierarchy. However, some virulence factors such as pyocyanin have been reported to still be produced in lasR mutants under certain conditions. Interestingly, such mutants arise spontaneously under various conditions, including in the airways of cystic fibrosis patients. Using transcriptional lacZ reporters, LC/MS quantification and phenotypic assays, we have investigated the regulation of QS-controlled factors by the las system. Our results show that activity of the rhl system is only delayed in a lasR mutant, thus allowing the expression of multiple virulence determinants such as pyocyanin, rhamnolipids and C4-homoserine lactone (HSL) during the late stationary phase. Moreover, at this stage, RhlR is able to overcome the absence of the las system by activating specific LasR-controlled functions, including production of 3-oxo-C12-HSL and Pseudomonas quinolone signal (PQS). P. aeruginosa is thus able to circumvent the deficiency of one of its QS systems by allowing the other to take over. This work demonstrates that the QS hierarchy is more complex than the model simply presenting the las system above the rhl system.

scholarly journals Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2612-2619 ◽  
Author(s):  
Lisa K. Nelson ◽  
Genevieve H. D'Amours ◽  
Kimberley M. Sproule-Willoughby ◽  
Douglas W. Morck ◽  
Howard Ceri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Tissue Damage ◽  
Inflammatory Markers ◽  
Bacterial Colonization ◽  
Opportunistic Pathogen ◽  
Infection Model ◽  
Chronic Infections ◽  
Strain Pao1 ◽  
Rat Prostate

Pseudomonas aeruginosa frequently acts as an opportunistic pathogen of mucosal surfaces; yet, despite causing aggressive prostatitis in some men, its role as a pathogen in the prostate has not been investigated. Consequently, we developed a Ps. aeruginosa infection model in the rat prostate by instilling wild-type (WT) Ps. aeruginosa strain PAO1 into the rat prostate. It was found that Ps. aeruginosa produced acute and chronic infections in this mucosal tissue as determined by bacterial colonization, gross morphology, tissue damage and inflammatory markers. WT strain PAO1 and its isogenic mutant PAO-JP2, in which both the lasI and rhlI quorum-sensing signal systems have been silenced, were compared during both acute and chronic prostate infections. In acute infections, bacterial numbers and inflammatory markers were comparable between WT PA01 and PAO-JP2; however, considerably less tissue damage occurred in infections with PAO-JP2. Chronic infections with PAO-JP2 resulted in reduced bacterial colonization, tissue damage and inflammation as compared to WT PAO1 infections. Therefore, the quorum-sensing lasI and rhlI genes in Ps. aeruginosa affect acute prostate infections, but play a considerably more important role in maintaining chronic infections. We have thus developed a highly reproducible model for the study of Ps. aeruginosa virulence in the prostate.

scholarly journals Plantain Herb Extracts significantly attenuate the quorum sensing-controlled virulence factors and inhibit biofilm formation in Pseudomonas aeruginosa PAO1

2019 ◽  
Vol 78 ◽  
pp. 01004
Author(s):  
Shan Li ◽  
Jiangning Yao ◽  
Haoming Li
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Significant Inhibition ◽  
Control Group ◽  
Produce Cell ◽  
Group B ◽  
Herb Extracts

Pseudomonas aeruginosa is a Gram-negative organism that can survive under harsh conditions, and it is also an opportunistic pathogen that can produce cell-associated extracellular virulence factors. Several of these virulence factors have been demonstrated to be regulated by quorum sensing (QS). Plantain Herb has been used as antibacterial agents for many centuries in China. In this study, we analyzed Plantain Herb Extracts (PHE) at the concentration of 16 μg/mL (Group A, MIC), 8 μg/mL (Group B, 1/2 MIC) and 4 μg/mL (Group C, 1/4 MIC) for inhibition of the virulence factors production and biofilm formation in P. aeruginosa PAO1. The virulence factors included pyocyanin, rhamnolipids, protease and alginate. PHE showed significant inhibition of virulence factors as compared to the control group without interfering its growth. Thus, PHE might be a potent QS inhibitor and anti-biofilm agent in the treatment of Pseudomonas aeruginosa infections.

scholarly journals GidA Posttranscriptionally Regulates rhl Quorum Sensing in Pseudomonas aeruginosa

2009 ◽  
Vol 191 (18) ◽  
pp. 5785-5792 ◽  
Author(s):  
Rashmi Gupta ◽  
Timothy R. Gobble ◽  
Martin Schuster
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Flavin Adenine Dinucleotide ◽  
Skim Milk ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Trna Modification ◽  
Loss Of Function ◽  
Novel Genes ◽  
Lasa Protease

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa utilizes two interconnected acyl-homoserine lactone quorum-sensing (acyl-HSL QS) systems, LasRI and RhlRI, to regulate the expression of hundreds of genes. The QS circuitry itself is integrated into a complex network of regulation by other factors. However, our understanding of this network is still unlikely to be complete, as a comprehensive, saturating approach to identifying regulatory components has never been attempted. Here, we utilized a nonredundant P. aeruginosa PA14 transposon library to identify additional genes that regulate QS at the level of LasRI/RhlRI. We initially screened all 5,459 mutants for loss of function in one QS-controlled trait (skim milk proteolysis) and then rescreened attenuated candidates for defects in other QS phenotypes (LasA protease, rhamnolipid, and pyocyanin production) to exclude mutants defective in functions other than QS. We identified several known and novel genes, but only two novel genes, gidA and pcnB, affected all of the traits assayed. We characterized gidA, which exhibited the most striking QS phenotypes, further. This gene is predicted to encode a conserved flavin adenine dinucleotide-binding protein involved in tRNA modification. Inactivation of the gene primarily affected rhlR-dependent QS phenotypes such as LasA, pyocyanin, and rhamnolipid production. GidA affected RhlR protein but not transcript levels and also had no impact on LasR and acyl-HSL production. Overexpression of rhlR in a gidA mutant partially restored QS-dependent phenotypes. Taken together, these results indicate that GidA selectively controls QS gene expression posttranscriptionally via RhlR-dependent and -independent pathways.

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 PqsE Functions Independently of PqsR-Pseudomonas Quinolone Signal and Enhances the rhl Quorum-Sensing System

2008 ◽  
Vol 190 (21) ◽  
pp. 7043-7051 ◽  
Author(s):  
John M. Farrow ◽  
Zoe M. Sund ◽  
Matthew L. Ellison ◽  
Dana S. Wade ◽  
James P. Coleman ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Virulence Factors ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Chronic Infections ◽  
Signaling Systems ◽  
Sensing System ◽  
Pseudomonas Quinolone Signal ◽  
Quorum Sensing System ◽  
Hostile Environments

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute and chronic infections in immunocompromised individuals. This gram-negative bacterium produces a battery of virulence factors that allow it to infect and survive in many different hostile environments. The control of many of these virulence factors falls under the influence of one of three P. aeruginosa cell-to-cell signaling systems. The focus of this study, the quinolone signaling system, functions through the Pseudomonas quinolone signal (PQS), previously identified as 2-heptyl-3-hydroxy-4-quinolone. This signal binds to and activates the LysR-type transcriptional regulator PqsR (also known as MvfR), which in turn induces the expression of the pqsABCDE operon. The first four genes of this operon are required for PQS synthesis, but the fifth gene, pqsE, is not. The function of the pqsE gene is not known, but it is required for the production of multiple PQS-controlled virulence factors and for virulence in multiple models of infection. In this report, we show that PqsE can activate PQS-controlled genes in the absence of PqsR and PQS. Our data also suggest that the regulatory activity of PqsE requires RhlR and indicate that a pqsE mutant can be complemented for pyocyanin production by a large excess of exogenous N-butyryl homoserine lactone (C4-HSL). Finally, we show that PqsE enhances the ability of Escherichia coli expressing RhlR to respond to C4-HSL. Overall, our data lead us to conclude that PqsE functions as a regulator that is independent of PqsR and PQS but dependent on the rhl quorum-sensing system.

scholarly journals Inhibition of Quorum Sensing in Pseudomonas aeruginosa by N-Acyl Cyclopentylamides

2007 ◽  
Vol 73 (10) ◽  
pp. 3183-3188 ◽  
Author(s):  
Takenori Ishida ◽  
Tsukasa Ikeda ◽  
Noboru Takiguchi ◽  
Akio Kuroda ◽  
Hisao Ohtake ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Homoserine Lactone ◽  
Ring Structure ◽  
Response Regulators ◽  
Maximal Inhibition ◽  
Sensing Systems ◽  
Reporter Assays

ABSTRACT N-Octanoyl cyclopentylamide (C8-CPA) was found to moderately inhibit quorum sensing in Pseudomonas aeruginosa PAO1. To obtain more powerful inhibitors, a series of structural analogs of C8-CPA were synthesized and examined for their ability to inhibit quorum sensing in P. aeruginosa PAO1. The lasB-lacZ and rhlA-lacZ reporter assays revealed that the chain length and the ring structure were critical for C8-CPA analogs to inhibit quorum sensing. N-Decanoyl cyclopentylamide (C10-CPA) was found to be the strongest inhibitor, and its concentrations required for half-maximal inhibition for lasB-lacZ and rhlA-lacZ expression were 80 and 90 μM, respectively. C10-CPA also inhibited production of virulence factors, including elastase, pyocyanin, and rhamnolipid, and biofilm formation without affecting growth of P. aeruginosa PAO1. C10-CPA inhibited induction of both lasI-lacZ by N-(3-oxododecanoyl)-l-homoserine lactone (PAI1) and rhlA-lacZ by N-butanoyl-l-homoserine lactone (PAI2) in the lasI rhlI mutant of P. aeruginosa PAO1, indicating that C10-CPA interferes with the las and rhl quorum-sensing systems via inhibiting interaction between their response regulators (LasR and RhlR) and autoinducers.

scholarly journals Evolution of the quorum sensing regulon in cooperating populations of Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Nicole E Smalley ◽  
Amy L Schaefer ◽  
Kyle L Asfahl ◽  
Crystal Perez ◽  
E Peter Greenberg ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Cell Communication ◽  
Opportunistic Pathogen ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Rna Seq ◽  
Bacterial Strains ◽  
Communication And Coordination

The bacterium Pseudomonas aeruginosa is an opportunistic pathogen and it thrives in many different saprophytic habitats. In this bacterium acyl-homoserine lactone quorum sensing (QS) can activate expression of over 100 genes, many of which code for extracellular products. P. aeruginosa has become a model for studies of cell-cell communication and coordination of cooperative activities. We hypothesized that long-term growth of bacteria under conditions where only limited QS-controlled functions were required would result in a reduction in the size of the QS-controlled regulon. To test this hypothesis, we grew P. aeruginosa for about 1000 generations in a condition in which expression of QS-activated genes is required for growth. We compared the QS regulons of populations after about 35 generations to those after about 1000 generations in two independent lineages by using quorum quenching and RNA-seq technology. In one evolved lineage the number of QS-activated genes identified was reduced by about 70% and in the other by about 45%. Our results lend important insights about the variations in the number of QS-activated genes reported for different bacterial strains and, more broadly, about the environmental histories of P. aeruginosa.

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