Researchers have discovered how a toxin from a common gut bacterium damages colon cells and promotes cancer. The finding, published in Nature, reveals that the toxin binds to claudin-4 before attacking the cells' protective barrier. A decoy protein developed by the team blocked the toxin in mice.
A multi-institutional team led by Johns Hopkins researchers solved a 15-year mystery about the toxin BFT produced by Bacteroides fragilis. The bacterium is found in up to 20 percent of healthy people, but certain strains trigger inflammation and tumors.
The study shows BFT must attach to the protein claudin-4 to reach and cut E-cadherin, which maintains the colon barrier. Senior author Cynthia Sears said the identification of the receptor opens doors to new detection and therapy approaches.
Using a CRISPR screen and structural biology, the team confirmed the binding and created a soluble claudin-4 decoy that protected mice from damage. Further work is needed to determine the exact structure and develop therapies.
The research received support from the National Institutes of Health and other institutions.
