Disruption of riboflavin biosynthesis in mycobacteria establishes riboflavin pathway intermediates as key precursors of MAIT cell agonists.

ABSTRACT: Mucosal-associated invariant T (MAIT) cells exhibit an intrinsic ability to recognize and respond to microbial infections. The semi-invariant antigen recognition receptor of MAIT cells specifically detects the non-polymorphic antigen-presenting molecule, major histocompatibility complex class I-related protein 1 (MR1), which primarily binds riboflavin-derived metabolites of microbial origin. To further interrogate the dependence of these antigens on riboflavin biosynthesis in mycobacteria, we deleted individual genes in the riboflavin biosynthesis pathways in Mycobacterium smegmatis (Msm) and Mycobacterium tuberculosis (Mtb) and evaluated the impact thereof on MAIT cell activation. Blocking the early steps of the pathway by deletion of RibA2 or RibG profoundly reduced, but did not complete

SUBMITTER: Chengalroyen MD 

PROVIDER: S-EPMC12240317 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature