National Institute of Allergy and Infectious Diseases 5R01AI179807-03

Harnessing commensal redox metabolism in infection prevention

This award funds research to study how commensal and pathogen redox metabolism in the gut affects infection by Clostridioides difficile, aiming to develop interventions to prevent and treat infections by targeting nutrient interactions.

Description

Many gut-infecting bacterial pathogens undergo growth expansion in the gut lumen as part of the virulence, and as supported by their underlying metabolism. Commensal metabolism in the gut provides an opportunity to impede these processes by depriving pathogens of growth-promoting nutrients. Using the amino acid and carbohydrate-fermenting pathogen Clostridioides difficile, we will evaluate how redox metabolism of target carbon sources by the pathogen and commensals can enhance or limit its ability to colonize and infect the gut. Analyses will leverage innovative approaches to track nutrient flow among pathogen, commensal, and host tissues. Studies will further perturb host environments using carbon sources that are fermented by the pathogen, protective commensals, or both, to assess their role in disease pathogenesis and progression. Findings will inform small molecule and bacteriotherapeutic interventions in disease prevention and treatment.

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