Reported by ScienceDaily
For nearly two decades, scientists have known that a common gut bacterium can produce a toxin that damages the colon and helps drive the formation of tumors. What they could not explain was how the toxin first attaches to intestinal cells and begins its attack. Now, researchers have uncovered that missing step, revealing a surprising vulnerability that could lead to new ways of protecting the colon.
The breakthrough comes from a team led by scientists at the Johns Hopkins Kimmel Cancer Center, its Bloomberg~Kimmel Institute for Cancer Immunotherapy, and the Johns Hopkins University School of Medicine. Their findings, published in Nature , identify a protein called claudin-4 as the essential docking point for a bacterial toxin known as BFT.
Even more promising, the researchers have already used this discovery to develop a molecular decoy that intercepts the toxin before it can damage colon cells. The strategy successfully protected mice from the toxin's harmful effects, suggesting a possible new approach to preventing bacterial damage associated with colorectal cancer. The research received partial support from the National Institutes of Health.
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"We've made several attempts over time to identify the receptor, so this is an exciting moment," says senior author Cynthia Sears, M.D., Bloomberg~Kimmel Professor of Cancer Immunotherapy and professor of medicine at Johns Hopkins. "Understanding how bacterial toxins work can open doors to new approaches for detection and therapy for associated diseases, including diarrhea, colorectal cancer and bloodstream infections."
The investigation centers on Bacteroides fragilis , a bacterium that can be found in the intestines of up to 20% of healthy people. Although the presence of this bacterium does not automatically mean someone will develop cancer, certain strains produce a powerful toxin capable of disrupting the colon's protective lining, causing inflammation, and encouraging tumor growth.
The toxin, known as B. fragilis toxin or BFT, has been under investigation for years. In a landmark 2009 study published in Nature Medicine , Sears and her colleagues demonstrated that the toxin could promote the development of colon tumors. Their work helped establish an important connection between toxin-producing gut bacteria, chronic inflammation, and colorectal cancer.
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