Diggle Stephen P, Matthijs Sandra, Wright Victoria J, Fletcher Matthew P, Chhabra Siri Ram, Lamont Iain L, Kong Xiaole, Hider Robert C, Cornelis Pierre, Cámara Miguel, Williams Paul
Institute of Infection, Immunity & Inflammation, Centre for Biomolecular Sciences, University Park, University of Nottingham, Nottingham NG7 2RD, United Kingdom.
Chem Biol. 2007 Jan;14(1):87-96. doi: 10.1016/j.chembiol.2006.11.014.
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.
铜绿假单胞菌产生2-庚基-3-羟基-4(1H)-喹诺酮(PQS),这是一种群体感应(QS)信号,可调节众多毒力基因,包括参与铁摄取的基因。生物物理分析表明,2-烷基-3-羟基-4-喹诺酮在生理pH值下与铁(III)形成复合物。2-甲基-3-羟基-4-喹诺酮铁(III)复合物的总稳定常数在pH 7.4时为logβ(3)=36.2,pFe(3+)值为16.6。发现PQS通过至少三种不同的信号通路发挥作用,并且其前体2-庚基-4-喹诺酮(HHQ)本身不形成铁复合物,但被发现可作为一种自诱导分子发挥作用。当将PQS提供给无法产生绿脓菌素或绿螯铁菌素的铜绿假单胞菌突变体时,PQS与细胞膜结合并抑制细菌生长,这一发现揭示了PQS在铁截留方面的次要功能,以促进铁载体介导的铁传递。