Scientists find how gut bacterium triggers colon cancer
Researchers have identified a protein that acts as a docking point for a toxin produced by Bacteroides fragilis.
Scientists at Johns Hopkins have identified the mechanism by which a common gut bacterium can trigger colorectal cancer, according to a report by The Tribune. The study reveals that the bacterium, Bacteroides fragilis, produces a toxin known as BFT that damages the colon's protective lining and promotes tumour formation.
The research team, which included scientists from the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins University School of Medicine, identified the protein claudin-4 as the essential docking point for the BFT toxin. For nearly two decades, researchers knew the toxin caused damage but could not explain how it first attached to intestinal cells.
To find the link, Maxwell White, an M.D./Ph.D. candidate in the laboratory of senior author Cynthia Sears, led a genome-wide CRISPR screening effort. The team switched off genes in colon epithelial cells to see which were necessary for the toxin to attach. When the gene for claudin-4 was disabled, the BFT could no longer bind to the colon cells.
Sears, a professor of medicine at Johns Hopkins, said that understanding how bacterial toxins work could lead to new approaches for the detection and therapy of diseases including colorectal cancer and diarrhoea. The researchers have already used the discovery to develop a molecular decoy that intercepts the toxin.
The study found that the BFT toxin must first latch onto claudin-4 before it can attack E-cadherin, a protein that helps maintain the colon's protective barrier. The research received partial support from the National Institutes of Health.