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The end of an old hypothesis: the pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from Fatty acids, not 3-ketofatty acids

Dulcey, Carlos Eduardo; Dekimpe, Valérie; Fauvelle, David-Alexandre; Milot, Sylvain; Groleau, Marie-Christine; Doucet, Nicolas; Rahme, Laurence G.; Lépine, François; Déziel, Éric (2013). The end of an old hypothesis: the pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from Fatty acids, not 3-ketofatty acids Chemistry and Biology , vol. 20 , nº 12. p. 1481-1491. DOI: 10.1016/j.chembiol.2013.09.021.

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Résumé

Groups of pathogenic bacteria use diffusible signals to regulate their virulence in a concerted manner. Pseudomonas aeruginosa uses 4-hydroxy-2-alkylquinolines (HAQs), including 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), as unique signals. We demonstrate that octanoic acid is directly incorporated into HHQ. This finding rules out the long-standing hypothesis that 3-ketofatty acids are the precursors of HAQs. We found that HAQ biosynthesis, which requires the PqsABCD enzymes, proceeds by a two-step pathway: (1) PqsD mediates the synthesis of 2-aminobenzoylacetate (2-ABA) from anthraniloyl-coenzyme A (CoA) and malonyl-CoA, then (2) the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC produces HHQ, the direct precursor of PQS. PqsB is tightly associated with PqsC and required for the second step. This finding uncovers promising targets for the development of specific antivirulence drugs to combat this opportunistic pathogen

Type de document:
Mots-clés libres: L-HOMOSERINE LACTONES, QUINOLONE SIGNAL, AERUGINOSA VIRULENCE, BIOSYNTHESIS, PATHOGENICITY, INTERFERENCE, PATHOGENESIS, GENES, 2,4-DIHYDROXYQUINOLINE, 2-AMINOACETOPHENONE
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 30 avr. 2014 13:31
Dernière modification: 20 nov. 2015 14:47
URI: http://espace.inrs.ca/id/eprint/2193

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