Ben May Department for Cancer Research, University of Chicago, 929 E., 57th St., Chicago, IL 60637, USA.
Biochem Biophys Res Commun. 2010 Apr 2;394(2):254-9. doi: 10.1016/j.bbrc.2010.02.091. Epub 2010 Feb 25.
Gastrointestinal (GI) anthrax, caused by the bacterial infection of Bacillus anthracis, posts a significant bioterrorism threat by its relatively high mortality rate in humans. Different from inhalational anthrax by the route of infection, accumulating evidence indicates the bypass of vegetative bacteria across GI epithelium is required to initiate GI anthrax. Previously, we reported that purified anthrolysin O (ALO), instead of tripartite anthrax edema and lethal toxins, is capable of disrupting gut epithelial tight junctions and barrier function in cultured cells. Here, we show that ALO can disrupt intestinal tissue barrier function in an ex vivo mouse model. To explore the effects of ALO in a cell culture model of B. anthracis infection, we showed that anthrax bacteria can effectively reduce the monolayer integrity of human Caco-2 brush-border expressor (C2BBE) cells based on the reduced transepithelial resistance and the increased leakage of fluorescent dye. This disruption is likely caused by tight junction dysfunction observed by the reorganization of the tight junction protein occludin. Consequently, we observe significant passage of vegetative anthrax bacteria across C2BBE cells. This barrier disruption and bacterial crossover requires ALO since ALO-deficient B. anthracis strains fail to induce monolayer dysfunction and allow the passage of anthrax bacteria. Together these findings point to a pivotal role for ALO within the establishment of GI anthrax infection and the initial bypass of the epithelial barrier.
胃肠道（GI）炭疽病是由炭疽杆菌细菌感染引起的，其在人类中的死亡率相对较高，因此构成了重大的生物恐怖主义威胁。与通过感染途径引起的吸入性炭疽病不同，越来越多的证据表明，需要绕过 GI 上皮的营养细菌才能引发 GI 炭疽病。先前，我们报道了纯化的炭疽溶素 O（ALO），而不是三部分炭疽水肿和致死毒素，能够破坏培养细胞中的肠道上皮紧密连接和屏障功能。在这里，我们表明 ALO 可以破坏体内外小鼠模型中的肠道组织屏障功能。为了在炭疽杆菌感染的细胞培养模型中探索 ALO 的作用，我们表明炭疽细菌可以有效降低基于跨上皮电阻降低和荧光染料泄漏增加的人 Caco-2 刷状边界表达（C2BBE）细胞单层完整性。这种破坏可能是由于紧密连接蛋白闭合蛋白的重排观察到紧密连接功能障碍引起的。因此，我们观察到营养炭疽细菌明显穿过 C2BBE 细胞。这种屏障破坏和细菌交叉需要 ALO，因为 ALO 缺陷型炭疽杆菌菌株不能诱导单层功能障碍并允许炭疽细菌通过。这些发现共同指出 ALO 在建立 GI 炭疽感染和上皮屏障初始旁路中的关键作用。
