Physiological role of RpoS-controlled functions of Escherichia coli

增加我们对细菌基因在营养剥夺或其他应激反应中表达的知识对于理解细菌生理和环境适应的基本方面至关重要。近年来，人们对一个关键的保守调节因子RpoS有了很多了解，RpoS是大量应激诱导基因表达所必需的，但仍有许多未解之谜。我们对RpoS控制的基因的功能还不完全了解。为了解决这个问题，我们将使用遗传和分子生物学工具来检查我们分离的rpos依赖基因的表达。通过同时描述许多rpos依赖基因的特征，我们将了解这些基因作为一类与正常生长所需的所谓管家基因有何不同。除了表征rpos依赖基因外，我们还将研究先前关于赖氨酸脱羧酶、转醛缩酶和过氧化氢酶表达的研究中出现的具体问题。这些固定特异性基因中的每一个在帮助细胞适应应激条件方面可能都很重要，因为我们发现它们只在细胞处于饥饿状态时的固定阶段表达——它们在正常条件下不表达。我们还将研究RpoS中选择的突变如何对细菌细胞的整体适应性做出贡献，并将使用代谢物分析来发现RpoS如何影响在次优生长条件下维持的细菌的代谢物通量。这些研究将扩展我们对有助于细菌持续存在和生存的因素的认识。

Increasing our knowledge regarding bacterial genes that are expressed in response to nutrient deprivation or other stresses is crucial for understanding basic aspects of bacterial physiology and environmental adaptation. In recent years, much has been learned about a key conserved regulator, RpoS, that is required for the expression of a large number of stress-induced genes but many unanswered questions remain. We do not have a full understanding of the function of genes controlled by RpoS. To address this, we will use genetic and molecular biology tools to examine the expression of RpoS-dependent genes that we have isolated. By simultaneously characterizing many RpoS-dependent genes, we will learn how these genes differ as a class from so-called housekeeping genes that are required for normal growth. In addition to characterizing RpoS-dependent genes, we will investigate specific questions that have arisen from our previous studies regarding lysine decarboxylase, transaldolase and catalase expression. Each of these stationary-specific genes are probably important in helping the cell adapt to stress conditions since we have found that they are expressed only in stationary phase when cells are in a starved state--they are not expressed under normal conditions. We will also examine how selected mutations in RpoS contribute to the overall fitness of the bacterial cell and will use metabolite analysis to discover how RpoS affects metabolite flux in bacteria maintained under suboptimal growth conditions. These studies will extend our knowledge of factors that contribute to bacterial persistence and survival.