The McbR transcription factor links intracellular folate pool to virulence in enteric pathogens

While the impact of environmental cues on virulence has been extensively studied, direct sensing of metabolic intermediates to inform virulence expressions is less understood. Sudden competition with the resident microbiota in the case of an infection is guaranteed to have a massive impact on the bacteria’s central metabolism, which may be used as a cue for the expression of virulence factors.

Here, we identify how fluctuations in the intracellular folate pool can affect expression of virulence factor in enterohemorrhagic E. coli (EHEC). Using transcriptomics, mutagenesis, and ligand-binding assays, we demonstrate that EHEC’s type III secretion system is repressed when the bacteria’s folate biosynthetic pathway is pharmacologically disrupted, and that this effect is mediated by two regulatory proteins: PurR and McbR.