General Information:

Id: 2,214
Diseases: Pseudomonas aeruginosa diseases
pathogen-host system
Pseudomonas aeruginosa/mammalia
review
Reference: Dubern JF and Diggle SP(2008) Quorum sensing by 2-alkyl-4-quinolones in Pseudomonas aeruginosa and other bacterial species. Mol Biosyst 4: 882-888 [PMID: 18704225]

Interaction Information:

Comment The QS system consists of two N-acylhomoserine lactone (AHL) regulatory circuits (las and rhl) linked to a 2-alkyl-4-quinolone (AQ) system.
Formal Description
Interaction-ID: 18613

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

affects_activity of

process

PQS quorum sensing

Comment In the las system, the lasI gene product directs the synthesis of N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), which interacts with the transcriptional regulator LasR and activates target promoters.
Formal Description
Interaction-ID: 18614

gene/protein

lasI

increases_quantity of

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

Comment In the las system, the lasI gene product directs the synthesis of N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), which interacts with the transcriptional regulator LasR and activates target promoters.
Formal Description
Interaction-ID: 18615

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

increases_activity of

gene/protein

lasR

Drugbank entries Show/Hide entries for lasR
Comment In the rhl system, rhlI directs the synthesis of N-(butanoyl)-L-homoserine lactone (C4-HSL), which interacts with the cognate regulator RhlR and activates target gene promoters.
Formal Description
Interaction-ID: 18616

gene/protein

rhlI

increases_quantity of

drug/chemical compound

N-Butyryl-HSL

Comment In the rhl system, rhlI directs the synthesis of N-(butanoyl)-L-homoserine lactone (C4-HSL), which interacts with the cognate regulator RhlR and activates target gene promoters.
Formal Description
Interaction-ID: 18617

drug/chemical compound

N-Butyryl-HSL

increases_activity of

gene/protein

rhlR

Comment PQS belongs to the AQ (2-alkyl-4-quinolones) family of compounds. In addition to PQS, other major molecules produced by P . aeruginosa, which belong to this family, include 2-heptyl-4-quinolone (HHQ), 2-nonyl-4-quinolone (NHQ) and 2-heptyl-4-quinolone N-oxide (HHQNO).
Formal Description
Interaction-ID: 18618

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

affects_activity of

process

PQS quorum sensing

Comment PQS belongs to the AQ (2-alkyl-4-quinolones) family of compounds. In addition to PQS (2-heptyl-3-hydroxy-4-quinolone signaling), other major molecules produced by P . aeruginosa, which belong to this family, include 2-heptyl-4-quinolone (HHQ), 2-nonyl-4-quinolone (NHQ) and 2-heptyl-4-quinolone N-oxide (HHQNO).
Formal Description
Interaction-ID: 18619

drug/chemical compound

2-Nonyl-4-hydroxyquinoline, NHQ

affects_activity of

process

PQS quorum sensing

Comment PQS belongs to the AQ (2-alkyl-4-quinolones) family of compounds. In addition to PQS, other major molecules produced by P . aeruginosa, which belong to this family, include 2-heptyl-4-quinolone (HHQ), 2-nonyl-4-quinolone (NHQ) and 2-heptyl-4-quinolone N-oxide (HHQNO).
Formal Description
Interaction-ID: 18620

drug/chemical compound

2-Heptyl-4-quinolone N-oxide, HHQNO

affects_activity of

process

PQS quorum sensing

Comment Anthranilate is a precursor for PQS. The anthranilate synthases are encoded by phnAB located adjacent to the pqsABCDE operon and these were shown to be part of the main metabolic pathway that provides anthranilate for PQS biosynthesis since phnAB is co-regulated with pqsABCDEoperon .
Formal Description
Interaction-ID: 18621

gene/protein

phnA

increases_quantity of

drug/chemical compound

Anthranilate

Drugbank entries Show/Hide entries for phnA
Comment Anthranilate is a precursor for PQS. The anthranilate synthases are encoded by phnAB located adjacent to the pqsABCDE operon and these were shown to be part of the main metabolic pathway that provides anthranilate for PQS biosynthesis since phnAB is co-regulated with pqsABCDEoperon .
Formal Description
Interaction-ID: 18623

gene/protein

phnB

increases_quantity of

drug/chemical compound

Anthranilate

Comment Anthranilate is a precursor for PQS. In addition to phnAB the three genes (kynA, kynB, and kynU) of the anthranilate branch of the kynurenine (kyn) pathway, which convert tryptophan to anthranilate, are present in P. aeruginosa.
Formal Description
Interaction-ID: 18635

gene/protein

kynA

increases_quantity of

drug/chemical compound

Anthranilate

Comment Anthranilate is a precursor for PQS. In addition to phnAB the three genes (kynA, kynB, and kynU) of the anthranilate branch of the kynurenine (kyn) pathway, which convert tryptophan to anthranilate, are present in P. aeruginosa.
Formal Description
Interaction-ID: 18642

gene/protein

kynB

increases_quantity of

drug/chemical compound

Anthranilate

Comment Anthranilate is a precursor for PQS. In addition to phnAB the three genes (kynA, kynB, and kynU) of the anthranilate branch of the kynurenine (kyn) pathway, which convert tryptophan to anthranilate, are present in P. aeruginosa.
Formal Description
Interaction-ID: 18644

gene/protein

kynU

increases_quantity of

drug/chemical compound

Anthranilate

Drugbank entries Show/Hide entries for kynU
Comment The presence of two independent pathways leading to anthranilate synthesis, which is the direct precursor in AQ (2-alkyl-4-quinolones) biosynthesis in P. aeruginosa implies that anthranilate is an important metabolite for the pathogenesis of P. aeruginosa.
Formal Description
Interaction-ID: 18646

drug/chemical compound

Anthranilate

affects_activity of

process

P. aeruginosa infection

Comment Anthranilate is converted by the pqsABCD gene products into HHQ (2-heptyl-4-quinolone), the precursor of PQS.
Formal Description
Interaction-ID: 18664

drug/chemical compound

Anthranilate

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

Comment Anthranilate is converted by the pqsABCD gene products into HHQ (2-heptyl-4-quinolone), the precursor of PQS.
Formal Description
Interaction-ID: 18665

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

increases_quantity of

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

Comment Anthranilate is converted by the pqsABCD gene products into HHQ (2-heptyl-4-quinolone), the precursor of PQS.
Formal Description
Interaction-ID: 18666

gene/protein

pqsA

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

Comment Anthranilate is converted by the pqsABCD gene products into HHQ (2-heptyl-4-quinolone), the precursor of PQS.
Formal Description
Interaction-ID: 18667

gene/protein

pqsB

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

Comment Anthranilate is converted by the pqsABCD gene products into HHQ (2-heptyl-4-quinolone), the precursor of PQS.
Formal Description
Interaction-ID: 18668

gene/protein

pqsC

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

Comment Anthranilate is converted by the pqsABCD gene products into HHQ (2-heptyl-4-quinolone), the precursor of PQS.
Formal Description
Interaction-ID: 18669

gene/protein

pqsD

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

Comment HHQ can be passed between cells and converted intracellularly into PQS through the action of PqsH, a probable FAD-dependent monoxygenase.
Formal Description
Interaction-ID: 18670

gene/protein

pqsH

increases_quantity of

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

Comment The transcription of the pqsH gene was shown to be positively controlled by LasR, providing a link between the AHL (Acyl-homoserine lactone) and AQ (2-alkyl-4-quinolones) quorum sensing systems .
Formal Description
Interaction-ID: 18671

gene/protein

lasR

increases_expression of

gene/protein

pqsH

Drugbank entries Show/Hide entries for lasR
Comment The regulation of the AQ (2-alkyl-4-quinolones) biosynthetic genes including the phnAB and pqsABCDE operons, occurs through a LysR family transcriptional regulator called PqsR (MvfR), which is positively controlled by LasR/3-oxo-C12-HSL.
Formal Description
Interaction-ID: 18672

gene/protein

mvfR

affects_expression of

gene/protein

phnA

Drugbank entries Show/Hide entries for phnA
Comment The regulation of the AQ (2-alkyl-4-quinolones) biosynthetic genes including the phnAB and pqsABCDE operons, occurs through a LysR family transcriptional regulator called PqsR (MvfR), which is positively controlled by LasR/3-oxo-C12-HSL.
Formal Description
Interaction-ID: 18673

gene/protein

mvfR

affects_expression of

gene/protein

phnB

Comment The regulation of the AQ (2-alkyl-4-quinolones) biosynthetic genes including the phnAB and pqsABCDE operons ,occurs through a LysR family transcriptional regulator called PqsR (MvfR), which is positively controlled by LasR/3-oxo-C12-HSL.
Formal Description
Interaction-ID: 18675

gene/protein

mvfR

affects_expression of

gene/protein

pqsA

Comment The regulation of the AQ (2-alkyl-4-quinolones) biosynthetic genes including the phnAB and pqsABCDE operons, occurs through a LysR family transcriptional regulator called PqsR (MvfR), which is positively controlled by LasR/3-oxo-C12-HSL.
Formal Description
Interaction-ID: 18676

gene/protein

mvfR

affects_expression of

gene/protein

pqsB

Comment The regulation of the AQ (2-alkyl-4-quinolones) biosynthetic genes including the phnAB and pqsABCDE operons, occurs through a LysR family transcriptional regulator called PqsR (MvfR), which is positively controlled by LasR/3-oxo-C12-HSL.
Formal Description
Interaction-ID: 18677

gene/protein

mvfR

affects_expression of

gene/protein

pqsC

Comment The regulation of the AQ (2-alkyl-4-quinolones) biosynthetic genes including the phnAB and pqsABCDE operons, occurs through a LysR family transcriptional regulator called PqsR (MvfR), which is positively controlled by LasR/3-oxo-C12-HSL.
Formal Description
Interaction-ID: 18678

gene/protein

mvfR

affects_expression of

gene/protein

pqsD

Comment PqsR binds the promoter of pqsABCDE but this binding increases dramatically in the presence of PQS, suggesting that PQS acts as a PqsR co-inducer.
Formal Description
Interaction-ID: 18679

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

increases_activity of

gene/protein

mvfR

Comment HHQ can also potentiate PqsR binding to the pqsABCDE promoter. Not only that, PQS is fully dispensable, as a pqsH mutant which produces HHQ but no PQS displayed normal PqsR-dependent gene expression and virulence.
Formal Description
Interaction-ID: 18680

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

increases_activity of

gene/protein

mvfR

Comment It has been established that PQS regulates the RhlI/R system. PQS positively regulates rhlI expression, thus influencing C4-HSL accumulation.
Formal Description
Interaction-ID: 18684

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

increases_expression of

gene/protein

rhlI

Comment pqsABCDE expression depends on the ratio between the two AHL molecules, 3-oxo-C12-HSL having a positive effect, and C4-HSL having a negative effect and that pqsR was a target for a negative regulation by rhl system. Las and rhl systems act antagonistically on pqsR regulation.
Formal Description
Interaction-ID: 18685

gene/protein

lasR

increases_activity of

gene/protein

mvfR

Drugbank entries Show/Hide entries for lasR
Comment pqsABCDE expression depends on the ratio between the two AHL molecules, 3-oxo-C12-HSL having a positive effect, and C4-HSL having a negative effect and that pqsR was a target for a negative regulation by rhl system. Las and rhl systems act antagonistically on pqsR regulation.
Formal Description
Interaction-ID: 18686

gene/protein

rhlR

decreases_activity of

gene/protein

mvfR

Comment The biosurfactant rhamnolipid produced by P. aeruginosa greatly increases solubility of PQS in aqueous solution, resulting in an increase in PQS bioactivity.
Formal Description
Interaction-ID: 18687

cellular component

rhamnolipid

increases_activity of

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

Comment PQS has also been shown to be involved in biofilm formation.
Formal Description
Interaction-ID: 18711

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

affects_activity of

Comment In early immunological experiments, 3-oxo-C12-HSL was shown to suppress interleukin-12 (IL-12 ) and tumor necrosis factor alpha (TNF-alpha) secretion by LPS-stimulated macrophages and to eliminate T-cell proliferation.
Formal Description
Interaction-ID: 18776

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

decreases_quantity of

gene/protein

IL12

Comment In early immunological experiments, 3-oxo-C12-HSL was shown to suppress interleukin-12 (IL-12 ) and tumor necrosis factor alpha (TNF-alpha) secretion by LPS-stimulated macrophages and to eliminate T-cell proliferation.
Formal Description
Interaction-ID: 18809

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

decreases_quantity of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment In early immunological experiments, 3-oxo-C12-HSL was shown to suppress interleukin-12 (IL-12 ) and tumor necrosis factor alpha (TNF-alpha) secretion by LPS-stimulated macrophages and to eliminate T-cell proliferation.
Formal Description
Interaction-ID: 18810

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

decreases_activity of

Comment Dynorphin, a K-opioid which is released from intestinal mucosa following ischemia in mice, was demonstrated to stimulate expression of pqsABCDE, production of HHQNO, HHQ, and PQS, and in turn enhance virulence factor production including pyocyanin and LecA. This suggests that P. aeruginosa can respond to opioid compounds released during host stress by regulating key elements of the quorum sensing system resulting in enhanced virulence.
Formal Description
Interaction-ID: 18815

drug/chemical compound

Dynorphin

increases_quantity of

drug/chemical compound

2-Heptyl-3-hydroxy-4-quinolone, PQS

Comment Dynorphin, a K-opioid which is released from intestinal mucosa following ischemia in mice, was demonstrated to stimulate expression of pqsABCDE, production of HHQNO, HHQ, and PQS, and in turn enhance virulence factor production including pyocyanin and LecA. This suggests that P. aeruginosa can respond to opioid compounds released during host stress by regulating key elements of the quorum sensing system resulting in enhanced virulence.
Formal Description
Interaction-ID: 18816

drug/chemical compound

Dynorphin

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

Comment Dynorphin, a K-opioid which is released from intestinal mucosa following ischemia in mice, was demonstrated to stimulate expression of pqsABCDE, production of HHQNO, HHQ, and PQS, and in turn enhance virulence factor production including pyocyanin and LecA. This suggests that P. aeruginosa can respond to opioid compounds released during host stress by regulating key elements of the quorum sensing system resulting in enhanced virulence.
Formal Description
Interaction-ID: 18817

drug/chemical compound

Dynorphin

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone N-oxide, HHQNO

Comment Dynorphin, a K-opioid which is released from intestinal mucosa following ischemia in mice, was demonstrated to stimulate expression of pqsABCDE, production of HHQNO, HHQ, and PQS, and in turn enhance virulence factor production including pyocyanin and LecA. This suggests that P. aeruginosa can respond to opioid compounds released during host stress by regulating key elements of the quorum sensing system resulting in enhanced virulence.
Formal Description
Interaction-ID: 18819

drug/chemical compound

Dynorphin

increases_quantity of

gene/protein

lecA

Comment The galactophilic lectin LecA has been shown to be important for the full maturation of biofilms.
Formal Description
Interaction-ID: 18820

gene/protein

lecA

increases_activity of

Comment The regulation of the AQ (2-alkyl-4-quinolones) biosynthetic genes including the phnAB and pqsABCDE operons ,occurs through a LysR family transcriptional regulator called PqsR (MvfR), which is positively controlled by LasR/3-oxo-C12-HSL.
Formal Description
Interaction-ID: 19225

gene/protein

mvfR

affects_expression of

gene/protein

pqsE