The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment.
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.
Diggle
Stephen P
SP
Institute of Infection, Immunity & Inflammation, Centre for Biomolecular Sciences, University Park, University of Nottingham, Nottingham NG7 2RD, United Kingdom. steve.diggle@nottingham.ac.uk
Matthijs
Sandra
S
Wright
Victoria J
VJ
Fletcher
Matthew P
MP
Chhabra
Siri Ram
SR
Lamont
Iain L
IL
Kong
Xiaole
X
Hider
Robert C
RC
Cornelis
Pierre
P
Cámara
Miguel
M
Williams
Paul
P
D042462:4-Quinolones; D007501:Iron / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000502:physiology*; D015363:Quinolones; D053038:Quorum Sensing; D015398:Signal Transduction
C407944:2-heptyl-3-hydroxy-4-quinolone; C528166:2-heptyl-4-quinolone; D042462:4-Quinolones; D015363:Quinolones; D007501:Iron