The RidA examine deaminase links metabolism with virulence in Campylobacter jejuni

RidA 研究脱氨酶将空肠弯曲杆菌代谢与毒力联系起来

基本信息

批准号：
10039719
负责人：
Diana M. Downs
金额：
$ 22.65万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10039719
关键词：
Antibiotic Resistance Bacteria Biochemical Biochemical Genetics Biogenesis Bioinformatics Biological Assay Biological Models Biology Biophysics Birds C-terminal Campylobacter Campylobacter infection Campylobacter jejuni Chemicals Chickens Data Deaminase Disease Domestic Fowls Economic Burden Electron Microscopy Environment Enzymes Europe Exposure to Flagella Food Poisoning Gastrointestinal tract structure Genes Genetic Glycobiology Goals Growth Heme Hydrogen Peroxide In Vitro Infection Knowledge Life Link Mass Spectrum Analysis Metabolic Metabolic stress Metabolism Molecular Molecular Genetics Nature Nutrient Organism Pathogenicity Play Positioning Attribute Prevention Process Production Protein Family Proteins Pyridoxal Phosphate Quantitative Reverse Transcriptase PCR RNA Research Design Research Personnel Role Signal Transduction Site Source Stress Structure Temperature United States Virulence Virulence Factors Work base catalase cell injury cell motility cofactor diarrheal disease genetic approach glycosylation heme biosynthesis host colonization in vivo innovation insight interest multiple datasets mutant novel strategies pathogen pathogenic bacteria transcriptomics

项目摘要

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.

项目概要空肠弯曲菌是全世界腹泻病的主要原因，也是常见原因欧洲和美国食物中毒事件频发。虽然很少致命，但空肠弯曲菌引起的疾病可以 2015 年美国弯曲杆菌感染造成的经济负担为 19 亿美元并且正在上升。空肠弯曲菌是许多鸟类消化道的自然栖息者，占零售量的 10-100% 鸡肉被这种生物体污染。因此，常见的感染源是未正确处理的家禽。这种细菌具有多样化的新陈代谢，可以在多种环境中生存和生长。温度、pH 值、渗透条件和养分有效性。此外，感染机制和其毒力尚不清楚，因此控制起来很困难。这里提出的工作目标是了解空肠弯曲菌的毒力如何整合到代谢中可以控制的过程。生物学中保守的代谢策略以及获得的见解从模型系统中，提供了增进我们对一般代谢范式的理解的方法，包括那些有助于致病策略的。高度保守的 Rid 蛋白家族 (IPR006056) 是通过对该细菌的转录组学分析表明，与空肠弯曲菌的毒力有关，并且我们的将其与功能性鞭毛联系起来的初步工作。 RidA 是一种具有特定作用的烯胺脱氨酶控制代谢应激。越来越清楚的是，对病原体（例如空肠弯曲菌）的代谢过程的严格了解是有必要的。对于控制感染的努力至关重要。本提案的目标将通过化学、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。这里的工作是出于了解反应产生所产生的压力的愿望生长过程中的代谢物，这些活性物质如何损害细胞成分，以及损害的后果是病原菌的生长、定植和/或毒力。