Johns Hopkins Finds B. fragilis Toxin Binds Claudin-4, Blocking Damage in Mice
Updated
Updated · SciTechDaily · May 14
Johns Hopkins Finds B. fragilis Toxin Binds Claudin-4, Blocking Damage in Mice
1 articles · Updated · SciTechDaily · May 14
Nature published Johns Hopkins-led work showing Bacteroides fragilis toxin must bind the host receptor claudin-4 before it can damage colon cells—a missing step in a mechanism tied to colorectal tumor growth since 2009.
A genomewide CRISPR screen identified claudin-4 as the key receptor; when researchers removed it from colon epithelial cells, the toxin no longer bound and E-cadherin remained unaffected.
One-to-one binding between the toxin and claudin-4 was then confirmed in test-tube studies and examined in mouse gut models, revealing an unusual receptor-first mechanism for a protease toxin.
A soluble claudin-4 decoy diverted the toxin and protected mice from colon damage, pointing to potential biologic or small-molecule therapies for diarrhea, colorectal cancer and bloodstream infections linked to B. fragilis.
B. fragilis is present in up to 20% of healthy people, but researchers still have not captured the toxin-receptor structure experimentally after AI tools such as AlphaFold failed to fully resolve it.
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Claudin-4 Identified as the Key Receptor Linking Enterotoxigenic Bacteroides fragilis to Colorectal Cancer: Mechanism, Clinical Impact, and New Therapeutic Strategies (2026 Breakthrough)
Overview
A groundbreaking study published in May 2026 revealed how the Bacteroides fragilis toxin (BFT) from enterotoxigenic Bacteroides fragilis (ETBF) promotes colon cancer. Researchers discovered that claudin-4, a tight junction protein on colon cells, acts as the specific receptor for BFT. Binding to claudin-4 is the essential first step, allowing BFT to function as a metalloprotease and cleave E-cadherin, a key molecule for cell adhesion. This previously unknown pathway explains how ETBF disrupts the gut barrier, leading to inflammation and cancer, and provides new insights into the complex relationship between the gut microbiome and disease.