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

The Pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment
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DOI:
10.1016/j.chembiol.2006.11.014
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发表时间:
2007-01-01
影响因子:
--
通讯作者:
Williams, Paul
Williams, Paul
中科院分区:
生物1区
文献类型:
--
作者:
Diggle, Stephen P.;Matthijs, Sandra;Williams, Paul

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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,可调节许多毒力基因,包括参与铁清除的毒力基因。生物物理分析表明,2-烷基-3-羟基-4-喹诺酮在生理pH下与铁(III)形成络合物。2-甲基-3-羟基-4-喹诺酮铁(III)络合物的总体稳定常数为log β(3)= 36.2,pFe(3+)值在pH 7.4下为16.6。发现PQS通过至少三种不同的信号传导途径起作用,并且发现其不形成铁络合物的前体2-庚基-4-喹诺酮(HHQ)本身作为自诱导分子起作用。当将PQS提供给不能产生绿脓菌荧光素或绿脓菌螯铁蛋白的铜绿假单胞菌突变体时,PQS与细胞包膜相关并抑制细菌生长,这一发现揭示了PQS在铁截留中的辅助功能,以促进铁载体介导的铁递送。
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(ill) at physiological pH. The overall stability constant of 2-methyl-3-hydroxy4-quinolone iron(Ill) 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.