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都会响应环境刺激来调节消失的表达，但一个值得注意的例外是调节运动性的趋化系统。然而，对黄色粘球菌 Che3 化学感应系统的分析得出了令人惊讶的发现，即这种趋化性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 系统包含 CheA、CheB、CheR、CheW 的同源物和两个化学感受器 (MCP)，但该系统的输出相对于大肠杆菌中用于控制运动的原型来说是不寻常的。 Che3 系统的输出不是由 CheY 介导的，而是通过 CrdA（sigma54 依赖性转录激活因子 NtrC 家族的同源物）提供能量，从而影响基因表达。 M. xanthus Che3 系统的知识将对我们理解更广泛的双组分信号转导领域（从原核发育的控制到生物膜形成和抗生素耐药性）产生重要影响。该项目的总体目标是全面表征 M. xanthus Che3 系统组成的信号通路。为了了解基因表达的化学感应调节机制及其在 M. xanthus 发育中的作用，提出了四个具体目标：1）表征信号通路的磷酸中继组件，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）识别 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.