title: Functional genetic analysis reveals a 2-Alkyl-4-quinolone signaling system in the human pathogen Burkholderia pseudomallei and related bacteria.
abstract: Pseudomonas aeruginosa synthesizes diverse 2-alkyl-4(1H)-quinolones (AHQs), including the signaling molecule 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), via the pqsABCDE locus. By examining the genome databases, homologs of the pqs genes were identified in other bacteria. However, apart from P. aeruginosa, only Burkholderia pseudomallei and B. thailandensis contained a complete pqsA-E operon (termed hhqA-E). By introducing the B. pseudomallei hhqA and hhqE genes into P. aeruginosa pqsA and pqsE mutants, we show that they are functionally conserved and restore virulence factor and PQS production. B. pseudomallei, B. thailandensis, B. cenocepacia, and P. putida each produced 2-heptyl-4(1H)-quinolone (HHQ), but not PQS. Mutation of hhqA in B. pseudomallei resulted in the loss of AHQ production, altered colony morphology, and enhanced elastase production, which was reduced to parental levels by exogenous HHQ. These data reveal a role for AHQs in bacterial cell-to-cell communication beyond that seen in P. aeruginosa.
authors.affiliation: Institute of Infection, Immunity & Inflammation, Centre for Biomolecular Sciences, University Park, University of Nottingham, UK. steve.diggle@nottingham.ac.uk
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Diggle
authors.forename: Putthapoom
authors.initials: P
authors.lastname: Lumjiaktase
authors.forename: Francesca
authors.initials: F
authors.lastname: Dipilato
authors.forename: Klaus
authors.initials: K
authors.lastname: Winzer
authors.forename: Mongkol
authors.initials: M
authors.lastname: Kunakorn
authors.forename: David A
authors.initials: DA
authors.lastname: Barrett
authors.forename: Siri Ram
authors.initials: SR
authors.lastname: Chhabra
authors.forename: Miguel
authors.initials: M
authors.lastname: Cámara
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
mesh_terms: D016957:Burkholderia pseudomallei / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005798:Genes, Bacterial; D013058:Mass Spectrometry; D010196:Pancreatic Elastase / Q000096:biosynthesis; D015363:Quinolones / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D015363:Quinolones; D010196:Pancreatic Elastase