Vat-Mediated Mucus Penetration Enables Genotoxic Activity of .

Colibactin toxin-producing () strains are associated with the occurrence of colorectal cancer in humans. These strains induce DNA damage when in close contact with the cells of the intestinal epithelium. Therefore, maintaining the integrity of the mucus layer that covers the intestinal epithelial mucosa is crucial for counteracting the effects of colibactin. The Vat protein is a mucin protease capable of degrading MUC2 mucus proteins that was previously described in adherent and invasive strains. Our work shows that the gene is found in the genome of all strains isolated from patients with colon cancer. In mucus-producing HT29-16E cells, we demonstrated that the Vat protein of allows bacteria to penetrate mucus and to reach the epithelial cells. Cells infected with the strain show a reduction in γ-H2AX staining, a marker of DNA damage. Infection of mice with the strain or the mutant revealed that Vat enhances the ability of strains to colonize the intestinal mucosa and, in turn, their pro-carcinogenic effects. This study reveals that Vat promotes crossing of the intestinal mucus layer, gut colonization, and the carcinogenicity of .