Loss of riboflavin biosynthesis leads to accumulation of select aromatic amino acids and loss of infectivity in Mycobacterium tuberculosis

Riboflavin depletion in Mycobacterium tuberculosis strains with disrupted riboflavin biosynthesis causes aromatic amino acid accumulation and loss of infectivity in an aerosol mouse infection.

• Why it matters: Riboflavin biosynthesis is required for in vitro survival, but it was unclear whether host-available riboflavin can support in vivo persistence and infectivity.
• What they did: Using inducible CRISPR interference knockdown and targeted deletions of riboflavin genes (ribA2, ribG, ribH, ribC), the authors tested rescue by riboflavin versus flavin adenine dinucleotide or flavin mononucleotide and profiled metabolites after riboflavin removal.
• The result: Riboflavin rescued auxotrophy for all strains tested, uptake was not linked to proton motive force or ATP synthesis, riboflavin depletion was bacteriostatic up to 3 weeks, and ΔribC showed lack of infectivity in an aerosol mouse infection.

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