近日，美国约翰霍普金斯大学医学院教授Cynthia L. Sears及其小组的研究开发出了一种致癌细菌毒素结合claudin-4切割E-钙粘蛋白。相关论文于2026年4月22日发表在《自然》杂志上。

在这里，研究组通过全基因组CRISPR筛选鉴定了claudin-4作为BFT受体，并证明claudin-4结合促进BFT介导的细胞表面E-cadherin的裂解。他们的工作既揭示了BFT的作用机制，也为抗BFT疗法的发展开辟了道路，这可能证明了预防结直肠癌和治疗急性肠毒素脆弱杆菌感染的主题。

据悉，人类的结肠里寄居着数万亿的细菌，这些细菌在人类的健康和疾病中起着重要的作用。流行病学和实验研究表明，某些结肠细菌可以刺激结直肠癌的发生和发展。其中一种细菌，产肠毒素的脆弱拟杆菌，通过一种单一的毒素，即脆弱杆菌毒素（BFT）的作用来驱动结肠肿瘤的形成。BFT是一种金属蛋白酶，它与结肠上皮细胞受体结合，并与E-钙粘蛋白外域的分裂有关，导致上皮屏障破坏、炎症和细胞增殖增加。然而，BFT受体的身份尚不清楚，BFT引发的E-钙粘蛋白裂解的分子机制也不清楚。

附：英文原文

Title: A pro-carcinogenic bacterial toxin binds claudin-4 to cleave E-cadherin

Author: White, Maxwell T., Wang, Kang, Zhang, Hailong, Eckhard, Ulrich, Hullahalli, Karthik, Chen, Jason, Wu, Shaoguang, Geis, Abby L., Zhang, Jie, Queen, Jessica, Gomis-Ruth, F. Xavier, Waldor, Matthew K., Dong, Min, Sears, Cynthia L.

Issue&Volume: 2026-04-22

Abstract: The human colon is colonized by trillions of bacteria that play substantial roles in human health and disease1. Epidemiological and experimental studies suggest that certain colonic bacteria can stimulate the development and progression of colorectal cancer2. One such bacterium, enterotoxigenic Bacteroides fragilis, drives colon tumour formation through the action of a single toxin, the B. fragilis toxin (BFT)3,4. BFT is a metalloprotease that binds to a colonic epithelial cell receptor and causes cleavage of the E-cadherin ectodomain, leading to epithelial barrier disruption, inflammation and increased cellular proliferation4,5,6. However, the identity of the BFT receptor is unknown and the molecular mechanism of BFT-initiated E-cadherin cleavage is not well understood. Here we identify claudin-4 as a BFT receptor through a genome-wide CRISPR screen and demonstrate that claudin-4 binding promotes BFT-mediated cleavage of cell surface E-cadherin. Our work both sheds light on BFT’s mechanism of action and opens avenues for the development of anti-BFT therapies, which may prove useful for colorectal cancer prevention and treatment of acute enterotoxigenic B. fragilis infection.

DOI: 10.1038/s41586-026-10375-0

Source: https://www.nature.com/articles/s41586-026-10375-0