Chemistry & Biology 2007-01-01

The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment.

Stephen P Diggle, Sandra Matthijs, Victoria J Wright, Matthew P Fletcher, Siri Ram Chhabra, Iain L Lamont, Xiaole Kong, Robert C Hider, Pierre Cornelis, Miguel Cámara, Paul Williams

Index: Chem. Biol. 14 , 87-96, (2007)

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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.