Feedback control of the pleiotropic regulators and H-NS antagonists LeuO and RcsB-BglJ in Escherichia coli

H-NS在抑制水平获得的富含AT的DNA以及对各种胁迫条件和与寄主栖息地相关的环境变化的反应的基因方面发挥着重要作用。H-NS的沉默作用建立在富含AT的DNA上核蛋白复合体的形成基础上，并受到特异的基因调控和释放。在这个项目中，我们希望分析涉及LysR型转录因子LeuO和LuxR型转录因子YjjQ和BglJ的调节级联。LeuO和YjjQ分别是影响肠道沙门氏菌和禽致病性大肠杆菌毒力的重要转录因子。LeuO的表达是H-NS抑制的，并且是正向自动调节的，它抵消了H-NS介导的对yjjQ-bglJ操纵子的抑制。YjjQ和BglJ都与RCS膜和肽聚糖胁迫信号系统的反应调节因子RCSB相互作用。到目前为止，这些蛋白唯一已知的靶基因是H-NS抑制的BGL操纵子，其抑制被BglJ/RCSB异源二聚体解除。该项目的目的是研究(I)LeuO下调YjjQ-bglJ操纵子的分子机制，(Ii)BglJ和YjjQ在共生和致病的大肠杆菌中控制H-NS和其他位点的作用及其与RCS信号转导系统的关系。

H-NS has a major role in repression of horizontally acquired AT-rich DNA and of genes for responses to various stress conditions and changes in the environment associated with the host habitat. Silencing by H-NS is based on the formation of nucleoprotein complexes on AT-rich DNA, and is modulated and relieved locus specifically. In this project we wish to analyze a regulatory cascade that involves the LysR-type transcription factor LeuO and the LuxR-type transcription factors YjjQ and BglJ. LeuO and YjjQ are transcription factors important for virulence of Salmonella enterica and avian pathogenic Escherichia coli, respectively. LeuO, whose expression is H-NS-repressed and positively auto-regulated, counteracts the H-NS mediated repression of the yjjQ-bglJ operon. YjjQ and BglJ both interact with the response regulator RcsB of the Rcs membrane and peptidoglycan stress signaling system. The so far only known target gene of these proteins is the H-NS repressed bgl operon whose repression is relieved by the BglJ/RcsB heterodimer. The aims of the project are to characterize (i) the molecular mechanism underlying de-repression of the yjjQ-bglJ operon by LeuO and (ii) the role of BglJ and YjjQ in control of H-NS repressed and other loci and in their relation to the Rcs signal transduction system in commensal and pathogenic E.coli.