title: The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment.
abstract: Pseudomonas aeruginosa produces 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), a quorum-sensing (QS) signal that regulates numerous virulence genes including those involved in iron scavenging. Biophysical analysis revealed that 2-alkyl-3-hydroxy-4-quinolones form complexes with iron(III) at physiological pH. The overall stability constant of 2-methyl-3-hydroxy-4-quinolone iron(III) complex was log beta(3) = 36.2 with a pFe(3+) value of 16.6 at pH 7.4. PQS was found to operate via at least three distinct signaling pathways, and its precursor, 2-heptyl-4-quinolone (HHQ), which does not form an iron complex, was discovered to function as an autoinducer molecule per se. When PQS was supplied to a P. aeruginosa mutant unable to make pyoverdine or pyochelin, PQS associated with the cell envelope and inhibited bacterial growth, a finding that reveals a secondary function for PQS in iron entrapment to facilitate siderophore-mediated iron delivery.
authors.affiliation: Institute of Infection, Immunity & Inflammation, Centre for Biomolecular Sciences, University Park, University of Nottingham, Nottingham NG7 2RD, United Kingdom. steve.diggle@nottingham.ac.uk
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Diggle
authors.forename: Sandra
authors.initials: S
authors.lastname: Matthijs
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Wright
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fletcher
authors.forename: Siri Ram
authors.initials: SR
authors.lastname: Chhabra
authors.forename: Iain L
authors.initials: IL
authors.lastname: Lamont
authors.forename: Xiaole
authors.initials: X
authors.lastname: Kong
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.forename: Pierre
authors.initials: P
authors.lastname: Cornelis
authors.forename: Miguel
authors.initials: M
authors.lastname: Cámara
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
mesh_terms: D042462:4-Quinolones; D007501:Iron / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000502:physiology*; D015363:Quinolones; D053038:Quorum Sensing; D015398:Signal Transduction
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; C528166:2-heptyl-4-quinolone; D042462:4-Quinolones; D015363:Quinolones; D007501:Iron