General Information:

Id: 2,285
Diseases: Pseudomonas aeruginosa diseases
pathogen-host system
Pseudomonas aeruginosa/mammalia
review
Reference: Heeb S et al.(2011) Quinolones: from antibiotics to autoinducers. FEMS Microbiol. Rev. 35: 247-274 [PMID: 20738404]

Interaction Information:

Comment AQs (2-alkyl-4(1H)-quinolones) have a low aqueous solubility. Because of this hydrophobic nature, a high proportion of the AQs are associated with the bacterial outer membrane and with membrane vesicles (MVs). Of the total amount of PQS produced by P. aeruginosa PA14, around 80% appears to be contained within vesicles, in contrast with ~1% of either of the P. aeruginosa N-acyl-homoserine lactone (AHL)-based signal molecules N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL).
Formal Description
Interaction-ID: 19466

drug/chemical compound

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

is localized in

cellular component

bacterial outer membrane

Comment AQs (2-alkyl-4(1H)-quinolones) have a low aqueous solubility. Because of this hydrophobic nature, a high proportion of the AQs are associated with the bacterial outer membrane and with membrane vesicles (MVs). Of the total amount of PQS produced by P. aeruginosa PA14, around 80% appears to be contained within vesicles, in contrast with ~1% of either of the P. aeruginosa N-acyl-homoserine lactone (AHL)-based signal molecules N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL).
Formal Description
Interaction-ID: 19470

drug/chemical compound

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

is localized in

cellular component

bacterial membrane vesicle, MV

Comment The pqsL gene encodes a second, distinct monooxygenase that is required for the synthesis of HQNO and related N-oxides via oxidation of the quinolone ring nitrogen atom. HQNO is derived from the same starting products as HHQ, but utilizes the additional monooxygenase Pqs.
Formal Description
Interaction-ID: 19472

gene/protein

pqsL

increases_quantity of

drug/chemical compound

2-Heptyl-4-hydroxyquinoline N-oxide, HQNO

Comment Although the PqsE crystal structure is available, little knowledge has been gained about its exact function. The deletion of pqsE reduces the production of several virulence factors including pyocyanin, lectin and hydrogen cyanide (HCN), while overexpression of pqsE has the opposite effect.
Formal Description
Interaction-ID: 19476

gene/protein

pqsE

increases_quantity of

drug/chemical compound

Pyocyanine

Comment Although the PqsE crystal structure is available, little knowledge has been gained about its exact function. The deletion of pqsE reduces the production of several virulence factors including pyocyanin, lectin and hydrogen cyanide (HCN), while overexpression of pqsE has the opposite effect.
Formal Description
Interaction-ID: 19477

gene/protein

pqsE

increases_quantity of

gene/protein

lecA

Comment Although the PqsE crystal structure is available, little knowledge has been gained about its exact function. The deletion of pqsE reduces the production of several virulence factors including pyocyanin, lectin and hydrogen cyanide (HCN), while overexpression of pqsE has the opposite effect.
Formal Description
Interaction-ID: 19478

gene/protein

pqsE

increases_quantity of

drug/chemical compound

Hydrogen cyanide

Comment PqsE is not involved in AQ (2-alkyl-4(1H)-quinolones) biosynthesis, and appears to be a crucial element mediating the cellular response to PQS to achieve full virulence.
Formal Description
Interaction-ID: 19479

gene/protein

pqsE

affects_activity of

process

P. aeruginosa infection

Comment The activity of PqsE has also been reported to be dependent on RhlR, which acts downstream, but in synergy with PqsE.
Formal Description
Interaction-ID: 19480

gene/protein

rhlR

affects_activity of

gene/protein

pqsE

Comment The pqsH gene encodes a predicted FAD-dependent monooxygenase that hydroxylates the 3-carbon atom of HHQ in the final step of PQS biosynthesis.
Formal Description
Interaction-ID: 19483

gene/protein

pqsH

increases_quantity of

drug/chemical compound

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

Comment PqsH is regulated by LasR, but not by PqsR.
Formal Description
Interaction-ID: 19484

gene/protein

lasR

increases_expression of

gene/protein

pqsH

Drugbank entries Show/Hide entries for lasR
Comment PqsH is regulated by LasR, but not by PqsR.
Formal Description
Interaction-ID: 19486

gene/protein

mvfR

NOT affects_expression of

gene/protein

pqsH

Comment HHQ is not a precursor for HQNO.
Formal Description
Interaction-ID: 19508

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

NOT affects_quantity of

drug/chemical compound

2-Heptyl-4-hydroxyquinoline N-oxide, HQNO

Comment DHQ (2,4-dihydroxyquinoline), which technically is not an AQ (2-alkyl-4(1H)-quinolones), is produced by PqsD independent of PqsB and PqsC.
Formal Description
Interaction-ID: 19510

gene/protein

pqsD

increases_quantity of

drug/chemical compound

2,4-Dihydroxyquinoline, DHQ

independent of PqsB and PqsC
Comment LasR will induce the production of virulence factors such as elastase and pyoverdin, while RhlR will increase the production of rhamnolipid biosurfactants, cytotoxic lectins, pyocyanin and elastase, among other virulence factors.
Formal Description
Interaction-ID: 19513

gene/protein

lasR

increases_quantity of

gene/protein

lasB

Drugbank entries Show/Hide entries for lasR or lasB
Comment LasR will induce the production of virulence factors such as elastase and pyoverdin, while RhlR will increase the production of rhamnolipid biosurfactants, cytotoxic lectins, pyocyanin and elastase, among other virulence factors.
Formal Description
Interaction-ID: 19514

gene/protein

lasR

increases_quantity of

drug/chemical compound

Pyoverdine I

Drugbank entries Show/Hide entries for lasR
Comment LasR will induce the production of virulence factors such as elastase and pyoverdin, while RhlR will increase the production of rhamnolipid biosurfactants, cytotoxic lectins, pyocyanin and elastase, among other virulence factors.
Formal Description
Interaction-ID: 19515

gene/protein

rhlR

increases_quantity of

cellular component

rhamnolipid

Comment LasR will induce the production of virulence factors such as elastase and pyoverdin, while RhlR will increase the production of rhamnolipid biosurfactants, cytotoxic lectins, pyocyanin and elastase, among other virulence factors.
Formal Description
Interaction-ID: 19516

gene/protein

rhlR

increases_quantity of

drug/chemical compound

Pyocyanine

Comment LasR will induce the production of virulence factors such as elastase and pyoverdin, while RhlR will increase the production of rhamnolipid biosurfactants, cytotoxic lectins, pyocyanin and elastase, among other virulence factors.
Formal Description
Interaction-ID: 19517

gene/protein

rhlR

increases_quantity of

gene/protein

lasB

Drugbank entries Show/Hide entries for lasB
Comment HHQ (2-heptyl-4-quinolone) acts as an autoinducer independent of PQS (Pseudomonas quinolone signal) . Other AQs (2-alkyl-4(1H)-quinolones), such as NHQ (2-nonyl-4-hydroxyquinoline) can also activate PqsR and as such could potentially be considered as autoinducers, although not as potent as PQS.
Formal Description
Interaction-ID: 19520

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

increases_activity of

gene/protein

mvfR

Comment HHQ (2-heptyl-4-quinolone) acts as an autoinducer independent of PQS (Pseudomonas quinolone signal) . Other AQs (2-alkyl-4(1H)-quinolones), such as NHQ (2-nonyl-4-hydroxyquinoline) can also activate PqsR and as such could potentially be considered as autoinducers, although not as potent as PQS.
Formal Description
Interaction-ID: 19521

drug/chemical compound

2-Nonyl-4-hydroxyquinoline, NHQ

increases_activity of

gene/protein

mvfR

Comment HHQ (2-heptyl-4-quinolone) acts as an autoinducer independent of PQS (Pseudomonas quinolone signal) . Other AQs (2-alkyl-4(1H)-quinolones), such as NHQ (2-nonyl-4-hydroxyquinoline) can also activate PqsR and as such could potentially be considered as autoinducers, although not as potent as PQS.
Formal Description
Interaction-ID: 19522

drug/chemical compound

2-Nonyl-4-hydroxyquinoline, NHQ

affects_activity of

process

PQS quorum sensing

Comment HHQ (2-heptyl-4-quinolone) acts as an autoinducer independent of PQS (Pseudomonas quinolone signal) . Other AQs (2-alkyl-4(1H)-quinolones), such as NHQ (2-nonyl-4-hydroxyquinoline) can also activate PqsR and as such could potentially be considered as autoinducers, although not as potent as PQS.
Formal Description
Interaction-ID: 19523

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

affects_activity of

process

PQS quorum sensing

Comment HHQ (2-heptyl-4-quinolone) acts as an autoinducer independent of PQS (Pseudomonas quinolone signal) . Other AQs (2-alkyl-4(1H)-quinolones), such as NHQ (2-nonyl-4-hydroxyquinoline) can also activate PqsR and as such could potentially be considered as autoinducers, although not as potent as PQS.
Formal Description
Interaction-ID: 19524

drug/chemical compound

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

affects_activity of

process

PQS quorum sensing

Comment PQS positively controlled the expression of the lasB (elastase) gene. It was later shown that this effect was considerably enhanced when PQS and C4-HSL acted synergistically to upregulate lasB expression.
Formal Description
Interaction-ID: 19572

drug/chemical compound

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

increases_expression of

gene/protein

lasB

Drugbank entries Show/Hide entries for lasB
Comment PQS positively controlled the expression of the lasB (elastase) gene. It was later shown that this effect was considerably enhanced when PQS and C4-HSL acted synergistically to upregulate lasB expression.
Formal Description
Interaction-ID: 19573

drug/chemical compound

N-Butyryl-HSL

increases_expression of

gene/protein

lasB

Drugbank entries Show/Hide entries for lasB
Comment Addition of PQS upregulates the expression of lecA and pyocyanin production in a concentration-dependent manner.
Formal Description
Interaction-ID: 19574

drug/chemical compound

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

increases_expression of

gene/protein

lecA

Comment Addition of PQS upregulates the expression of lecA and pyocyanin production in a concentration-dependent manner.
Formal Description
Interaction-ID: 19575

drug/chemical compound

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

increases_quantity of

drug/chemical compound

Pyocyanine

Comment RhlR and RpoS are essential for lecA expression and addition of PQS failed to restore lecA transcription in rhlR or rpoS mutants, confirming the importance of these two regulators for lecA promoter activity.
Formal Description
Interaction-ID: 19576

gene/protein

rpoS

affects_expression of

gene/protein

lecA

Comment RhlR and RpoS are essential for lecA expression and addition of PQS failed to restore lecA transcription in rhlR or rpoS mutants, confirming the importance of these two regulators for lecA promoter activity.
Formal Description
Interaction-ID: 19577

gene/protein

rhlR

affects_expression of

gene/protein

lecA

Comment PQS, but not HHQ, induces the transcription of the small regulatory RNA RsmZ.
Formal Description
Interaction-ID: 19578

drug/chemical compound

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

increases_expression of

ncRNA/miRNA

rsmZ

Comment PQS, but not HHQ, induces the transcription of the small regulatory RNA RsmZ.
Formal Description
Interaction-ID: 19579

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

NOT increases_expression of

ncRNA/miRNA

rsmZ

Comment PtxR is a transcriptional regulator that positively affects the production of exotoxin A and negatively affects the production of pyocyanin.
Formal Description
Interaction-ID: 19586

gene/protein

ptxR

increases_expression of

gene/protein

toxA

Drugbank entries Show/Hide entries for toxA
Comment PtxR is a transcriptional regulator that positively affects the production of exotoxin A and negatively affects the production of pyocyanin.
Formal Description
Interaction-ID: 19587

gene/protein

ptxR

decreases_quantity of

drug/chemical compound

Pyocyanine

Comment PmpR, a protein of the YebC-like superfamily, binds to the pqsR promoter and affects its transcription negatively.
Formal Description
Interaction-ID: 19590

gene/protein

pmpR

decreases_expression of

gene/protein

mvfR

Comment PpyR (psl and pyoverdine operon regulator, PA2663) positively regulates exopolysaccharide and pyoverdine production.
Formal Description
Interaction-ID: 19591

gene/protein

ppyR

increases_quantity of

cellular component

psl-exopolysaccharide

Comment PpyR (psl and pyoverdine operon regulator, PA2663) positively regulates exopolysaccharide and pyoverdine production.
Formal Description
Interaction-ID: 19592

gene/protein

ppyR

increases_quantity of

drug/chemical compound

Pyoverdine I

Comment Clinical isolates from sputum in CF (cystic fibrosis) patients showed that they all produced PQS and also HHQ, HQNO, NQNO and UQNO. In addition, there was a correlation between the levels of PQS and the bacterial sample load.
Formal Description
Interaction-ID: 19608

process

P. aeruginosa infection, chronic

increases_quantity of

drug/chemical compound

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

in sputum of CF patients
Comment Clinical isolates from sputum in CF (cystic fibrosis) patients showed that they all produced PQS and also HHQ, HQNO, NQNO and UQNO. In addition, there was a correlation between the levels of PQS and the bacterial sample load.
Formal Description
Interaction-ID: 19609

process

P. aeruginosa infection, chronic

increases_quantity of

drug/chemical compound

2-Heptyl-4-quinolone, HHQ

in sputum of CF patients
Comment Clinical isolates from sputum in CF (cystic fibrosis) patients showed that they all produced PQS and also HHQ, HQNO, NQNO and UQNO. In addition, there was a correlation between the levels of PQS and the bacterial sample load.
Formal Description
Interaction-ID: 19610

process

P. aeruginosa infection, chronic

increases_quantity of

drug/chemical compound

2-Heptyl-4-hydroxyquinoline N-oxide, HQNO

in sputum of CF patients
Comment Clinical isolates from sputum in CF (cystic fibrosis) patients showed that they all produced PQS and also HHQ, HQNO, NQNO and UQNO. In addition, there was a correlation between the levels of PQS and the bacterial sample load.
Formal Description
Interaction-ID: 19611

process

P. aeruginosa infection, chronic

increases_quantity of

drug/chemical compound

2-Nonyl-4-hydroxyquinoline N-oxide, NQNO

in sputum of CF patients
Comment Clinical isolates from sputum in CF (cystic fibrosis) patients showed that they all produced PQS and also HHQ, HQNO, NQNO and UQNO. In addition, there was a correlation between the levels of PQS and the bacterial sample load.
Formal Description
Interaction-ID: 19612

process

P. aeruginosa infection, chronic

increases_quantity of

drug/chemical compound

2-Undecyl-4-hydroxyquinoline N-oxide, UQNO

in sputum of CF patients
Comment The expression of the phnAB genes is induced 14-22-fold, in line with the upregulation of the pqsABCDE operon (17-19-fold) in clinical isolates from sputum in CF (cystic fibrosis) patients compared with the expression of these genes in a morpholinepropanesulphonic acid-buffered glucose medium.
Formal Description
Interaction-ID: 19613

process

P. aeruginosa infection, chronic

increases_expression of

gene/protein

phnA

in sputum of CF patients
Drugbank entries Show/Hide entries for phnA
Comment The expression of the phnAB genes is induced 14-22-fold, in line with the upregulation of the pqsABCDE operon (17-19-fold) in clinical isolates from sputum in CF (cystic fibrosis) patients compared with the expression of these genes in a morpholinepropanesulphonic acid-buffered glucose medium.
Formal Description
Interaction-ID: 19614

process

P. aeruginosa infection, chronic

increases_expression of

gene/protein

phnB

in sputum of CF patients
Comment The expression of the phnAB genes is induced 14-22-fold, in line with the upregulation of the pqsABCDE operon (17-19-fold) in clinical isolates from sputum in CF (cystic fibrosis) patients compared with the expression of these genes in a morpholinepropanesulphonic acid-buffered glucose medium.
Formal Description
Interaction-ID: 19615

process

P. aeruginosa infection, chronic

increases_expression of

gene/protein

pqsA

in sputum of CF patients
Comment The expression of the phnAB genes is induced 14-22-fold, in line with the upregulation of the pqsABCDE operon (17-19-fold) in clinical isolates from sputum in CF (cystic fibrosis) patients compared with the expression of these genes in a morpholinepropanesulphonic acid-buffered glucose medium.
Formal Description
Interaction-ID: 19616

process

P. aeruginosa infection, chronic

increases_expression of

gene/protein

pqsB

in sputum of CF patients
Comment The expression of the phnAB genes is induced 14-22-fold, in line with the upregulation of the pqsABCDE operon (17-19-fold) in clinical isolates from sputum in CF (cystic fibrosis) patients compared with the expression of these genes in a morpholinepropanesulphonic acid-buffered glucose medium.
Formal Description
Interaction-ID: 19618

process

P. aeruginosa infection, chronic

increases_expression of

gene/protein

pqsC

in sputum of CF patients
Comment The expression of the phnAB genes is induced 14-22-fold, in line with the upregulation of the pqsABCDE operon (17-19-fold) in clinical isolates from sputum in CF (cystic fibrosis) patients compared with the expression of these genes in a morpholinepropanesulphonic acid-buffered glucose medium.
Formal Description
Interaction-ID: 19619

process

P. aeruginosa infection, chronic

increases_expression of

gene/protein

pqsD

in sputum of CF patients
Comment The expression of the phnAB genes is induced 14-22-fold, in line with the upregulation of the pqsABCDE operon (17-19-fold) in clinical isolates from sputum in CF (cystic fibrosis) patients compared with the expression of these genes in a morpholinepropanesulphonic acid-buffered glucose medium.
Formal Description
Interaction-ID: 19621

process

P. aeruginosa infection, chronic

increases_expression of

gene/protein

pqsE

in sputum of CF patients
Comment Farnesol, a sesquiterpene signal molecule produced by C. albicans, reduces the transcription of pqsA by interacting with PqsR, resulting in a decrease in both PQS and pyocyanin production.
Formal Description
Interaction-ID: 19631

drug/chemical compound

2-trans,6-trans-Farnesol

decreases_expression of

gene/protein

pqsA

Comment Farnesol, a sesquiterpene signal molecule produced by C. albicans, reduces the transcription of pqsA by interacting with PqsR, resulting in a decrease in both PQS and pyocyanin production.
Formal Description
Interaction-ID: 19632

drug/chemical compound

2-trans,6-trans-Farnesol

decreases_quantity of

drug/chemical compound

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

Comment Farnesol, a sesquiterpene signal molecule produced by C. albicans, reduces the transcription of pqsA by interacting with PqsR, resulting in a decrease in both PQS and pyocyanin production.
Formal Description
Interaction-ID: 19633

drug/chemical compound

2-trans,6-trans-Farnesol

decreases_quantity of

drug/chemical compound

Pyocyanine

Comment Farnesol, a sesquiterpene signal molecule produced by C. albicans, reduces the transcription of pqsA by interacting with PqsR, resulting in a decrease in both PQS and pyocyanin production.
Formal Description
Interaction-ID: 19634

drug/chemical compound

2-trans,6-trans-Farnesol

affects_activity of

gene/protein

mvfR