Gene regulation by alpha-hydroxyketone-mediated signaling in Legionella pneumophila

细菌通过对环境提示做出反应，并通过产生被称为自身诱导物的内源信号分子来调节基因表达。嗜肺军团菌含有群体军团菌LQS基因簇，编码自诱导合酶LqsA、同源感受器蛋白激酶LqsS和新的反应调节因子LqsR。LqsA是一种依赖于吡哆醛-5‘-磷酸的酶，可合成α-羟基酮信号分子家族成员LAI-1(军团菌自身诱导物-1，3-羟基十五烷-4-酮)。功能研究和转录组分析表明，lqsA、lqsS和lqsR基因调控嗜肺乳杆菌与宿主细胞的相互作用、胞外细丝和基因组的“适合岛”。该项目的目的是利用生化、遗传和细胞微生物方法对α-羟基酮介导的嗜肺乳杆菌基因调控进行详细的分子分析。具体地说，这一应用的重点是：(I)α-羟基酮介导的同源感受器激酶LqsS和LqsT的信号转导，(Ii)反应调节因子LqsR的功能和结构，以及(Iii)LAI-1和细胞外细丝的内源产生。

Bacteria regulate gene expression by responding to environmental cues and by producing endogenous signaling molecules termed autoinducers. The pathogenic bacterium Legionella pneumophila harbors the lqs (Legionella quorum sensing) gene cluster, which encodes the autoinducer synthase LqsA, the putative cognate sensor kinase LqsS and the novel response regulator LqsR. LqsA is a pyridoxal-5´-phosphate-dependent enzyme and synthesizes LAI-1 (Legionella autoinducer-1, 3-hydroxypentadecane-4-one), a member of the α-hydroxyketone signaling molecule family. Functional studies and transcriptome analysis revealed that the lqsA, lqsS and lqsR genes regulate L. pneumophila-host cell interactions, extracellular filaments and a genomic “fitness island”. The aims of this project are a detailed molecular analysis of α-hydroxyketone-mediated gene regulation in L. pneumophila using biochemical, genetic and cellular microbial approaches. Specifically, the following topics are the focus of this application: (i) α-hydroxyketone-mediated signal transduction by the homologous sensor kinases LqsS and LqsT, (ii) function and structure of the response regulator LqsR, and (iii) endogenous production of LAI-1 and extracellular filaments.