Anti-quorum sensing and antibiofilm potential of 1,8-cineole derived from Musa paradisiaca against Pseudomonas aeruginosa strain PAO1

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.

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Quorum Sensing Negatively Controls Type III Secretion Regulon Expression in Pseudomonas aeruginosa PAO1

Journal of Bacteriology ◽

10.1128/jb.187.11.3898-3902.2005 ◽

2005 ◽

Vol 187 (11) ◽

pp. 3898-3902 ◽

Cited By ~ 87

Author(s):

Sophie Bleves ◽

Chantal Soscia ◽

Patricia Nogueira-Orlandi ◽

Andrée Lazdunski ◽

Alain Filloux

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Type Iii Secretion ◽

Down Regulation ◽

Strain Pao1 ◽

Systematic Analysis ◽

Pseudomonas Aeruginosa Pao1 ◽

Type Iii

ABSTRACT A systematic analysis of the type III secretion (T3S) genes of Pseudomonas aeruginosa strain PAO1 revealed that they are under quorum-sensing control. This observation was supported by the down-regulation of the T3S regulon in the presence of RhlR-C4HSL and the corresponding advanced secretion of ExoS in a rhlI mutant.

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

Microbiology ◽

10.1099/mic.0.049338-0 ◽

2011 ◽

Vol 157 (7) ◽

pp. 2120-2132 ◽

Cited By ~ 123

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.

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Emergence of Secretion-Defective Sublines of Pseudomonas aeruginosa PAO1 Resulting from Spontaneous Mutations in the vfr Global Regulatory Gene

Applied and Environmental Microbiology ◽

10.1128/aem.02539-07 ◽

2008 ◽

Vol 74 (6) ◽

pp. 1902-1908 ◽

Cited By ~ 16

Author(s):

Áine Fox ◽

Dieter Haas ◽

Cornelia Reimmann ◽

Stephan Heeb ◽

Alain Filloux ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Extracellular Enzymes ◽

Spontaneous Mutation ◽

Regulatory Gene ◽

Selective Advantage ◽

Wild Type ◽

Strain Pao1 ◽

Cultivation In Vitro

ABSTRACT Pseudomonas aeruginosa undergoes spontaneous mutation that impairs secretion of several extracellular enzymes during extended cultivation in vitro in rich media, as well as during long-term colonization of the cystic fibrosis lung. A frequent type of strong secretion deficiency is caused by inactivation of the quorum-sensing regulatory gene lasR. Here we analyzed a spontaneously emerging subline of strain PAO1 that exhibited moderate secretion deficiency and partial loss of quorum-sensing control. Using generalized transduction, we mapped the secretion defect to the vfr gene, which is known to control positively the expression of the lasR gene and type II secretion of several proteases. We confirmed this secretion defect by sequencing and complementation of the vfr mutation. In a reconstruction experiment conducted with a 1:1 mixture of wild-type strain PAO1 and a vfr mutant of PAO1, we observed that the vfr mutant had a selective advantage over the wild type after growth in static culture for 4 days. Under these conditions, spontaneous vfr emerged in a strain PAO1 population after four growth cycles, and these mutants accounted for more than 40% of the population after seven cycles. These results suggest that partial or complete loss of quorum sensing and secretion can be beneficial to P. aeruginosa under certain environmental conditions.

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Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.6.1930-1933.2001 ◽

2001 ◽

Vol 45 (6) ◽

pp. 1930-1933 ◽

Cited By ~ 272

Author(s):

Kazuhiro Tateda ◽

Rachel Comte ◽

Jean-Claude Pechere ◽

Thilo Köhler ◽

Keizo Yamaguchi ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Virulence Factor ◽

Strain Pao1 ◽

Unknown Mechanism ◽

Factor Production ◽

Encoding Gene ◽

Encoding Genes ◽

Virulence Factor Production

ABSTRACT We report that 2 μg of azithromycin/ml inhibits the quorum-sensing circuitry of Pseudomonas aeruginosa strain PAO1. Addition of synthetic autoinducers partially restored the expression of the trancriptional activator-encoding geneslasR and rhlR but not that of the autoinducer synthase-encoding gene lasI. We propose that azithromycin interferes with the synthesis of autoinducers, by an unknown mechanism, leading to a reduction of virulence factor production.

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Utilization of Acyl-Homoserine Lactone Quorum Signals for Growth by a Soil Pseudomonad and Pseudomonas aeruginosa PAO1

Applied and Environmental Microbiology ◽

10.1128/aem.69.10.5941-5949.2003 ◽

2003 ◽

Vol 69 (10) ◽

pp. 5941-5949 ◽

Cited By ~ 233

Author(s):

Jean J. Huang ◽

Jong-In Han ◽

Lian-Hui Zhang ◽

Jared R. Leadbetter

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Atmospheric Pressure Chemical Ionization ◽

Homoserine Lactone ◽

Small Subunit ◽

Rrna Gene ◽

Ionization Mass ◽

Small Subunit Rrna ◽

Strain Pao1 ◽

Pressure Chemical Ionization

ABSTRACT Acyl-homoserine lactones (AHLs) are employed by several Proteobacteria as quorum-sensing signals. Past studies have established that these compounds are subject to biochemical decay and can be used as growth nutrients. Here we describe the isolation of a soil bacterium, Pseudomonas strain PAI-A, that degrades 3-oxododecanoyl-homoserine lactone (3OC12HSL) and other long-acyl, but not short-acyl, AHLs as sole energy sources for growth. The small-subunit rRNA gene from strain PAI-A was 98.4% identical to that of Pseudomonas aeruginosa, but the soil isolate did not produce obvious pigments or AHLs or grow under denitrifying conditions or at 42°C. The quorum-sensing bacterium P. aeruginosa, which produces both 3OC12HSL and C4HSL, was examined for the ability to utilize AHLs for growth. It did so with a specificity similar to that of strain PAI-A, i.e., degrading long-acyl but not short-acyl AHLs. In contrast to the growth observed with strain PAI-A, P. aeruginosa strain PAO1 growth on AHLs commenced only after extremely long lag phases. Liquid-chromatography-atmospheric pressure chemical ionization-mass spectrometry analyses indicate that strain PAO1 degrades long-acyl AHLs via an AHL acylase and a homoserine-generating HSL lactonase. A P. aeruginosa gene, pvdQ (PA2385), has previously been identified as being a homologue of the AHL acylase described as occurring in a Ralstonia species. Escherichia coli expressing pvdQ catalyzed the rapid inactivation of long-acyl AHLs and the release of HSL. P. aeruginosa engineered to constitutively express pvdQ did not accumulate its 3OC12HSL quorum signal when grown in rich media. However, pvdQ knockout mutants of P. aeruginosa were still able to grow by utilizing 3OC12HSL. To our knowledge, this is the first report of the degradation of AHLs by pseudomonads or other γ-Proteobacteria, of AHL acylase activity in a quorum-sensing bacterium, of HSL lactonase activity in any bacterium, and of AHL degradation with specificity only towards AHLs with long side chains.

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Virulence factors regulation by the quorum-sensing and Rsm systems in the marine strain Pseudomonas aeruginosa ID4365, a natural mutant in lasR

FEMS Microbiology Letters ◽

10.1093/femsle/fnaa092 ◽

2020 ◽

Vol 367 (12) ◽

Cited By ~ 1

Author(s):

Miguel Cocotl-Yañez ◽

Martín Paolo Soto-Aceves ◽

Abigail González-Valdez ◽

Luis Servín-González ◽

Gloria Soberón-Chávez

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Virulence Factors ◽

Reference Strain ◽

Ecological Niches ◽

Human Pathogen ◽

Strain Pao1 ◽

Opportunistic Human Pathogen ◽

Marine Strain

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen that is able to produce several virulence factors such as pyocyanin, rhamnolipids and elastase. In the clinical reference strain PAO1, synthesis of these virulence factors is regulated transcriptionally by quorum sensing (QS) and post-transcriptionally by the Rsm system. Herein, we investigated the role of these systems in the control of the pyocyanin, rhamnolipids and elastase production in the marine strain ID4365. We found that this strain carries a nonsense mutation in lasR that makes it a natural mutant in the Las QS system. However, its QS response is still functional with the Rhl system activating virulence factors synthesis. We found that the Rsm system affects virulence factors production, since overexpression of RsmA reduces pyocyanin production whereas RsmY overexpression increases its synthesis. Unexpectedly, and in contrast to the type strain PAO1, inactivation of rsmA increases pyocyanin but reduces elastase and rhamnolipids production by a reduction of RhlR levels. Thus, QS and Rsm systems are involved in regulating virulence factors production, but this regulation is different to the PAO1 strain even though their genomes are highly conserved. It is likely that these differences are related to the different ecological niches in which these strains lived.

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