Regulation of Stationary Phase in Escherichia coli

大肠杆菌固定相的调节

• 批准号: 7578838
• 负责人: Thomas J. Silhavy
• 金额: $ 28.53万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7578838
• 关键词: Address; Animals; Bacteria; Bacteria sigma factor KatF protein; Biochemical; Biology; Carbon; Cells; Computing Methodologies; Enterobacteriaceae; Escherichia; Escherichia coli; Genetic; Genetic Translation; Light; Mediating; Metabolism; Microbe; Molecular; Nitrogen; Nutrient; Orphan; Pathogenesis; Pathway interactions; Peptide Hydrolases; Phase; Phosphorus; Process; Proteins; Regulation; Sigma Factor; Signal Transduction; Source; Starvation; Testing; deprivation; genetic regulatory protein; insight; metabolomics; pathogen; response

DESCRIPTION (provided by applicant): Enteric bacteria such as Escherichia coli spend most of their lifetimes starved for one or more essential nutrients. To survive environmental challenges under starvation conditions these bacteria enter a non-growing state called stationary phase. The master regulator of stationary phase is the alternate primary sigma factor RpoS. In rapidly growing cells RpoS levels are low because the orphan response regulator SprE (RssB) targets RpoS for degradation by the CIpP/X protease. We have discovered that when bacteria are starved for carbon, RpoS levels increase because RpoS degradation stops. Starvation for phosphorus also results in elevated levels of RpoS, but in this case levels are elevated because of an increase in rpoS mRNA translation. In contrast starvation for nitrogen does not cause an increase in RpoS levels; rather, RpoS activity is increased. We propose a combination of genetic, biochemical, metabolomic, and computational methods to identify the key signaling and effector molecules that mediate these diverse responses to nutrient deprivation. Since RpoS is known to be important for the pathogenesis of certain bacteria, a detailed understanding of how bacteria enter and exit stationary phase may reveal chinks in the armor of these pathogens. In addition, because the pathways of central metabolism are conserved throughout biology, we think that the signals that trigger transition to a non-growing state may be conserved as well. Thus insights gained in bacteria may shed light on similar processes in eukaryotic microbes, and perhaps animal cells as well.

描述（由申请人提供）：肠道细菌（例如大肠杆菌）的大部分时间都花在一种或多种必需营养素上。为了在饥饿条件下应对环境挑战，这些细菌进入了一种称为固定相的非生长状态。固定相的主调节器是替代的主要Sigma因子RPO。在快速生长的细胞中，RPOS水平较低，因为孤儿反应调节剂SPRE（RSSB）靶向RPO，以通过CIPP/X蛋白酶降解。我们已经发现，当细菌因碳而饥饿时，RPOS水平会增加，因为RPOS降解停止。磷的饥饿还会导致RPO水平升高，但在这种情况下，由于RPOS mRNA翻译的增加，水平升高。相反，氮的饥饿并不会导致RPOS水平升高。相反，RPOS活动增加。我们提出了遗传，生化，代谢组和计算方法的结合，以鉴定介导这些对营养剥夺的各种反应的关键信号传导和效应分子。由于已知RPO对于某些细菌的发病机理很重要，因此对细菌如何进入和退出固定相的详细理解可能揭示了这些病原体的盔甲中的缝隙。此外，由于中央代谢的途径在整个生物学过程中都是保守的，因此我们认为触发过渡到非生长状态的信号也可以得到保存。因此，在细菌中获得的见解可能会揭示真核微生物中的类似过程，也许还可以揭示动物细胞。