Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent lon protease

Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent lon protease
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DOI:
10.1128/jb.01873-07
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发表时间:
2008-06-01
影响因子:
3.2
通讯作者:
Yamamoto, Tomoko
Yamamoto, Tomoko
中科院分区:
生物学3区
文献类型:
--
作者:
Takaya, Akiko;Tabuchi, Fumiaki;Yamamoto, Tomoko

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Lon 蛋白酶是 ATP 依赖性蛋白酶家族的成员,通过降解特定底物来调节许多细胞系统。在这里,我们证明 Lon 参与铜绿假单胞菌(一种机会性人类病原体)群体感应 (QS) 信号系统的调节。该生物体具有两个酰基高丝氨酸内酯 (HSL) 介导的 QS 系统:LasR/LasI 和 RhlR/RhlI。许多报告表明,这两个系统受到全球监管机构的监管和相互关联。我们发现 lon 破坏的细胞过量产生绿脓素,其生物合成依赖于 RhlR/RhlI 系统,并且转录调节因子 RhlR 的水平增加。 QS 系统按层次结构组织:RhlR/RhlI 系统从属于 LasR/LasI。为了阐明 Lon 负向调节 RhlR/RhlI 的机制,我们研究了 Ion 破坏对 LasR/LasI 系统的影响。我们发现 Lon 通过降解 LasI(一种 HSL 合酶)来抑制 LasR/LasI 的表达,从而导致 RhlR/RhlI 系统的负调节。 RhlR/RhlI 还显示出通过调节 RhlI(一种 HSL 合酶)而独立于 LasR/LasI 受到 Lon 的调节。鉴于这些发现,表明 Lon 蛋白酶是铜绿假单胞菌中 HSL 介导的 QS 系统的强大负调节因子。
Lon protease, a member of the ATP-dependent protease family, regulates numerous cellular systems by degrading specific substrates. Here, we demonstrate that Lon is involved in the regulation of quorum-sensing (QS) signaling systems in Pseudomonas aeruginosa, an opportunistic human pathogen. The organism has two acyl-homoserine lactone (HSL)-mediated QS systems, LasR/LasI and RhlR/RhlI. Many reports have demonstrated that these two systems are regulated and interconnected by global regulators. We found that lon-disrupted cells overproduce pyocyanin, the biosynthesis of which depends on the RhlR/RhlI system, and show increased levels of a transcriptional regulator, RhlR. The QS systems are organized hierarchically: the RhlR/RhlI system is subordinate to LasR/LasI. To elucidate the mechanism by which Lon negatively regulates RhlR/RhlI, we examined the effect of Ion disruption on the LasR/LasI system. We found that Lon represses the expression of LasR/LasI by degrading LasI, an HSL synthase, leading to negative regulation of the RhlR/RhlI system. RhlR/RhlI was also shown to be regulated by Lon independently of LasR/LasI via regulation of RhlI, an HSL synthase. In view of these findings, it is suggested that Lon protease is a powerful negative regulator of both HSL-mediated QS systems in P. aeruginosa.