Abstract
The opportunistic pathogen Pseudomonas aeruginosa produces a large array of 4-hydroxy-2-alkylquinolines (HAQs). These compounds were analyzed by LC/MS, using positive electrospray ionization, in the culture supernatant of strain PA14. Fifty-six HAQs and related compounds were detected and their [M + H](+) ions were further analyzed by collision induced dissociation (CID). These HAQs were grouped into five different series based on the presence of an hydrogen or hydroxyl group at the 3 position, an N-oxide group in place of the quinoline nitrogen, and an unsaturation on their alkyl side chain. Two new analogs of 3,4-dihydroxy-2 heptylquinoline, the Pseudomonas quinolone signal (PQS), were found with an alkyl chain longer by one and two methylene groups. Moreover, two additional series of compounds were identified in which a saturated or unsaturated alkyl side chain is located at the 3 position along with an hydroxyl group at the 3 position and a ketone at the 2 position. No HAQ N-oxides, nor any compounds from the latter two series, were detected in a pqsL mutant derivative of PA14, indicating that this gene is involved in the biosynthesis of these compounds. This work demonstrates the large repertoire of HAQ and HAQ-related compounds produced by P. aeruginosa, and provides insight into N-oxides biosynthesis and confirm the hypothesis that N-oxides are the precursors of compounds from Series 6 and 7.
MeSH Terms
Molecular Structure
Pseudomonas aeruginosa/chemistry,metabolism
Quinolones/analysis,chemistry,metabolism
Spectrometry, Mass, Electrospray Ionization
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Milot Sylvain
Déziel Eric
He Jianxin
Rahme Laurence G
References (20)
20 references, click to expand
-
A broad-host-range Flp-FRT recombination system for site-specific excision of chromosomally-located DNA sequences: application for isolation of unmarked Pseudomonas aeruginosa mutants.
Gene. 1998 May 28;212(1):77-86
PMID: 9661666
-
A bacterial cell to cell signal in the lungs of cystic fibrosis patients.
FEMS Microbiol Lett. 2002 Sep 24;215(1):41-6
PMID: 12393198
-
Secondary metabolites from fluorescent pseudomonads.
FEMS Microbiol Rev. 1993 Apr;10(3-4):209-28
PMID: 8318257
-
Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants.
J Bacteriol. 2002 Dec;184(23):6481-9
PMID: 12426335
-
Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing.
Annu Rev Genet. 2001;35:439-68
PMID: 11700290
-
Antibiotic substances produced by Pseudomonas aeruginosa; syntheses of Pyo Ib, Pyo Ic, and Pyo III.
J Biol Chem. 1952 May;196(1):331-40
PMID: 12980974
-
[Biosynthesis of 2-n-alkyl-4-hydroxyquinoline derivates (pseudane) in Pseudomonas aeruginosa].
Eur J Biochem. 1971 Feb 1;18(3):391-400
PMID: 5542949
-
Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa.
J Bacteriol. 2002 Dec;184(23):6472-80
PMID: 12426334
-
Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication.
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1339-44
PMID: 14739337
-
Antibiotic metabolites from a marine pseudomonad.
Antimicrob Agents Chemother. 1977 Mar;11(3):411-4
PMID: 324390
-
Common virulence factors for bacterial pathogenicity in plants and animals.
Science. 1995 Jun 30;268(5219):1899-902
PMID: 7604262
-
Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa.
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11229-34
PMID: 10500159
-
2-Heptyl-4-hydroxyquinoline N-oxide, an antistaphylococcal agent produced by Pseudomonas aeruginosa.
J Antimicrob Chemother. 1992 Nov;30(5):615-23
PMID: 1493979
-
Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa.
Proc Natl Acad Sci U S A. 2001 Sep 25;98 (20):11633-7
PMID: 11573001
-
Quinolones from a bacterium and tyrosine metabolites from its host sponge, Suberea creba from the Coral Sea.
J Mar Biotechnol. 1998 Aug;6(3):136-41
PMID: 9701634
-
Structure of a naturally occurring antagonist of dihydrostreptomycin.
Biochem J. 1956 May;63(1):124-30
PMID: 13315257
-
Inhibition of cytochrome systems of heart muscle and certain bacteria by the antagonists of dihydrostreptomycin: 2-alkyl-4-hydroxyquinoline N-oxides.
Biochem J. 1956 May;63(1):130-7
PMID: 13315258
-
Lung infections associated with cystic fibrosis.
Clin Microbiol Rev. 2002 Apr;15(2):194-222
PMID: 11932230
-
Rapid identification of 4-hydroxy-2-alkylquinolines produced by Pseudomonas aeruginosa using gas chromatography-electron-capture mass spectrometry.
J Chromatogr B Biomed Appl. 1995 Feb 17;664(2):458-62
PMID: 7780603
-
A stable isotope dilution assay for the quantification of the Pseudomonas quinolone signal in Pseudomonas aeruginosa cultures.
Biochim Biophys Acta. 2003 Jun 20;1622(1):36-41
PMID: 12829259