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响应于环境刺激调节gone表达，一个显著的例外是调节运动性的趋化性系统。然而，对黄色粘球菌中Che 3化学感受系统的分析导致了令人惊讶的发现，该趋化性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系统包含CheA、切布、CheR、CheW和两种化学感受器（MCP）的同源物，但该系统的输出相对于在大肠杆菌中发现的原型是不寻常的。大肠杆菌中进行控制的运动。Che3系统的输出不是由CheY介导的，而是通过CrdA（σ 54依赖性转录激活因子的NtrC家族的同源物）馈送，从而影响基因表达。M的知识。Xanthus Che3系统的建立将对我们理解从原核生物发育到生物膜形成和抗生素抗性等更广泛的双组分信号转导领域具有重要意义。该项目的总体目标是充分表征包括M. xanthus Che 3系统。了解化学感受性调控基因表达的机制及其在M. xanthus，提出了四个具体目标：1）表征信号通路的磷酸化组分，2）表征受体信号复合物，3）分析甲基化依赖适应的作用，以及4）识别由Che 3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.