Chemosensory Regulation of Bacterial Gene Expression

描述(申请人提供)：在所有已知的双组分系统中，绝大多数都是对环境刺激的反应来调节失活的表达，一个值得注意的例外是调节运动的趋化系统。然而，对黄色粘球菌的Che3化学感觉系统的分析导致了一个令人惊讶的发现，即这个趋化性样的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。尽管Che3系统包括CheA、Cheb、Cher、Chew和两个化学受体(MCP)的同源物，但该系统的输出与在大肠杆菌中发现的用于控制运动的原型相比是不寻常的。Che3系统的输出不是由Chey介导的，而是通过CRDA来调节的，CRDA是NTRC依赖于sigma54的转录激活剂家族的同源物，因此影响基因的表达。对黄花分枝杆菌Che3系统的了解将对我们理解两组分信号转导的更广泛领域具有重要意义，从控制原核生物的发育到生物膜的形成和抗生素耐药性。该项目的总体目标是充分描述组成黄花链霉菌Che3系统的信号通路。为了了解化学感觉调控基因表达的机制及其在黄瓜生长发育中的作用，提出了四个具体的目标：1)鉴定信号通路的磷传递成分，2)鉴定受体信号复合体，3)分析甲基化依赖的适应的作用，4)鉴定由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.