Characterizing metabolic drivers of Clostridioides difficile infection with activity-based hydrazine probes.

ABSTRACT: Many enzymes require post-translational modifications or cofactor machinery for primary function. As these catalytically essential moieties are highly regulated, they act as dual sensors and chemical handles for context-dependent metabolic activity. Clostridioides difficile is a major nosocomial pathogen that infects the colon. Energy generating metabolism, particularly through amino acid Stickland fermentation, is central to colonization and persistence of this pathogen during infection. Here using activity-based protein profiling (ABPP), we revealed Stickland enzyme activity is a biomarker for C. difficile infection (CDI) and annotated two such cofactor-dependent Stickland reductases. We structurally characterized the cysteine-derived pyruvoyl cofactors of D-proline and gly

SUBMITTER: Bustin KA 

PROVIDER: S-EPMC9908766 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature