The RidA examine deaminase links metabolism with virulence in Campylobacter jejuni

项目摘要 空肠弯曲杆菌是世界范围内导致结肠炎的主要原因， 在欧洲和美国的食物中毒。虽然很少致命，但C.空肠可以是 2015年美国弯曲杆菌感染的经济负担为19亿美元 而且还在上升C.空肠是许多鸟类消化道的天然居民，并且在零售量的10-100%之间。 鸡肉被这种微生物污染了。因此，一个常见的感染源是准备不当的家禽。 这种细菌具有多样化的代谢，允许在具有多种微生物的环境中存活和生长。 温度、pH值、渗透条件和养分有效性。此外，感染机制和 对毒力的了解不多，因此难以控制。 本研究的目的是了解C.空肠被整合到代谢 可以控制的过程。在生物学中保守的代谢策略，以及获得的见解 从模型系统，提供手段，以促进我们的理解一般代谢范例，包括 那些有助于致病的策略。高度保守的Rid蛋白家族（IPR 006056）是 与C.空肠，如该细菌的转录组学分析所示，我们的 初步工作将其与功能鞭毛联系起来。RidA是一种烯胺脱氨酶， 控制代谢压力 越来越清楚的是，对病原体代谢过程的严格理解（例如，C.空肠）是 这对控制感染的努力至关重要。本提案的目标将通过以下方式实现： 化学、生物化学、生物物理、分子、遗传和生物信息学方法的创新组合。 这里的工作是出于理解反应性生产所产生的压力的愿望 生长过程中的代谢产物，这些反应性物质如何破坏细胞成分，以及 损害的后果是致病细菌的生长、定殖和/或毒力。

PROJECT SUMMARY The Campylobacter jejuni bacterium is a leading cause of diarrheal disease worldwide and a common cause of food poisoning in Europe and the United States. Although rarely fatal, disease caused C. jejuni can be debilitating, and the economic burden of Campylobacter infections in the United States in 2015 was $1.9 billion and is rising. C. jejuni is a natural inhabitant of the digestive tract of many birds, and between 10-100% of retail chicken is contaminated with this organism. Thus, a common source of infection is incorrectly prepared poultry. This bacterium has a diverse metabolism that allows survival and growth in environments with a variety of temperatures, pHs, osmotic conditions, and nutrient availabilities. Further, the mechanism of infection and virulence is not well understood, making its control difficult. The goal of the work proposed here is to understand how virulence of C. jejuni is integrated into metabolic processes that can be controlled. Metabolic strategies that are conserved across biology, and insights obtained from model systems, provide the means to advance our understanding of general metabolic paradigms, including those that contribute to pathogenic strategies. The highly conserved Rid family of proteins (IPR006056) is implicated in the virulence of C. jejuni as indicated by transcriptomics analyses of this bacterium, and our preliminary work associating it with functional flagella. RidA is an enamine deaminase with characterized roles in controlling metabolic stress. It is becoming clear that a rigorous understanding of metabolic processes of pathogens (e.g., C. jejuni) is critical to efforts aimed at controlling infections. The goals of this proposal will be accomplished through the innovative combination of chemical, biochemical, biophysical, molecular, genetic and bioinformatics approaches. The work here is motivated by the desire to understand the stress generated by the production of reactive metabolites during growth, how such reactive species can damage cellular components, and what the consequences of the damage are for growth, colonization and/or virulence of a pathogenic bacterium.