The RidA examine deaminase links metabolism with virulence in Campylobacter jejuni

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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.