The RidA examine deaminase links metabolism with virulence in Campylobacter jejuni

项目总结 空肠弯曲杆菌是世界范围内腹泻疾病的主要原因，也是一种常见的原因。 欧洲和美国的食物中毒。虽然很少致命，但由空肠弯曲菌引起的疾病可能是 令人虚弱，2015年美国弯曲杆菌感染造成的经济负担为19亿美元 而且还在上升。空肠弯曲菌是许多鸟类消化道的天然居住者，零售业的10%-100% 鸡肉被这种微生物污染了。因此，一个常见的感染源是未正确烹调的家禽。 这种细菌具有多样化的新陈代谢，使其能够在各种环境中生存和生长 温度、PHS、渗透条件和营养可利用性。此外，感染的机制和 毒力还没有被很好地理解，这使得它的控制变得困难。 这项工作的目标是了解空肠弯曲菌的毒力是如何整合到代谢中的。 可以控制的过程。跨生物学保守的新陈代谢策略，以及获得的见解 从模型系统中，提供了促进我们对一般代谢范例的理解的方法，包括 那些有助于致病策略的人。高度保守的RID蛋白家族(IPR006056)是 通过对这种细菌的转录组学分析表明，与空肠弯曲菌的毒力有关，以及我们的 将其与功能性鞭毛联系起来的初步工作。RIDA是一种烯胺脱氨酶，具有独特的作用 在控制代谢压力方面。 越来越清楚的是，对病原体(如空肠弯曲菌)代谢过程的严格理解是 对旨在控制感染的努力至关重要。这项提案的目标将通过 化学、生化、生物物理、分子、遗传和生物信息学方法的创新组合。 这项工作的动机是希望了解由反应性反应的产生产生的压力 生长过程中的代谢物，这些活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、定植和/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.