Chemosensory Regulation of Bacterial Gene Expression

描述（由申请人提供）：绝大多数已知的双组分系统在响应环境刺激时调节gone表达，但有一个值得注意的例外是调节运动的趋化系统。然而，对黄粘球菌Che3化学感觉系统的分析导致了令人惊讶的发现，这种趋化样信号转导系统影响发育调节的gone表达，而不影响运动性或趋化性。虽然Che3系统包括CheA、CheB、CheR、CheW和两种化学感受器（MCPs）的同源物，但该系统的输出与大肠杆菌中发现的控制运动的原型不同。Che3系统的输出不是由CheY介导的，而是通过CrdA（一种依赖于sigma54转录激活因子的NtrC家族的同系物）供能，从而影响基因表达。了解M. xanthus Che3系统将对我们理解更广泛的双组分信号转导领域具有重要意义，从原核生物发育的控制到生物膜的形成和抗生素耐药性。本项目的总体目标是充分表征由黄原草Che3系统组成的信号通路。为了了解化学感觉调控基因表达的机制及其在黄原草发育中的作用，提出了四个具体目标：1)表征信号通路中的磷接力组分，2)表征受体信号复合物，3)分析甲基化依赖性适应的作用，4)确定Che3系统控制的输出。

DESCRIPTION (provided by applicant): The vast majority of all known two-component systems regulate gone expression in response to environmental stimuli with one notable exception being the chemotaxis system that regulates motility. Analysis of the Che3 chemosensory system in Myxococcus xanthus led to the surprising discovery, however, that this chemotaxis-like signal transduction system affects developmentally regulated gone expression without affecting motility or chemotaxis. Although the Che3 system comprises homologs to CheA, CheB, CheR, CheW, and two chemoreceptors (MCPs), the output of the system is unusual with respect to the prototype found in E. coli for the control of motility. The output of the Che3 system is not mediated by CheY but feeds through CrdA, a homolog of the NtrC family of sigma54-dependent transcriptional activators and thereby affects gene expression. Knowledge of the M. xanthus Che3 system will have important implications for our understanding of the broader fields of two-component signal transduction ranging from the control of prokaryotic development to biofilm formation and antibiotic resistance. The overall goal of this project is to fully characterize the signaling pathway comprising the M. xanthus Che3 system. To understand the mechanism of chemosensory regulation of gene expression and its role in development of M. xanthus, four specific aims are proposed: 1) characterize the phosphorelay component of the signaling pathway, 2) characterize the receptor signaling complex, 3) analyze the role of methylation-dependent adaptation, and 4) identify the output controlled by the Che3 system.