Clostridium difficile toxin B induces apoptosis in intestinal cultured cells
Clostridium difficile toxin B induces apoptosis in intestinal cultured cells
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DOI：
10.1128/iai.66.6.2660-2665.1998
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发表时间：
1998-06-01
影响因子：
3.1
通讯作者：
Donelli, G
中科院分区：
文献类型：
--
作者：
Fiorentini, C;Fabbri, A;Donelli, G
厌氧细菌艰难梭菌的产毒菌株产生至少两种大的单链蛋白外毒素，参与抗生素相关性腹泻和结肠炎的发病机制。毒素A （CdA）是一种细胞毒性肠毒素，而毒素B （CdB）是一种更强效的细胞毒素，缺乏肠毒性活性。本研究处理了CdB，提供了第一个证据，表明肠细胞暴露于这种毒素表现出典型的凋亡特征，即处理过的细胞中有很大一部分表现出核断裂和染色质凝结。与超微结构数据一致，cdb处理的细胞显示出典型的细胞凋亡的流式细胞术标志，由一个明显的亚g峰组成。cdb诱导的凋亡反应是剂量和时间依赖的，而不仅仅是由于毒素的肌动蛋白破坏作用或随后的细胞锚定损伤。相反，CdB对Rho家族蛋白的抑制似乎在诱导肠细胞凋亡中起作用。细胞的起源和生长速度也可能是与这种反应相关的辅助因素。
Toxigenic strains of the anaerobic bacterium Clostridium difficile produce at least two large, single-chain protein exotoxins involved in the pathogenesis of antibiotic-associated diarrhea and colitis. Toxin A (CdA) is a cytotoxic enterotoxin, while toxin B (CdB) is a more potent cytotoxin lacking enterotoxic activity. This study dealt with CdB, providing the first evidence that intestinal cells exposed to this toxin exhibit typical features of apoptosis in that a significant proportion of the treated cells displayed nuclear fragmentation and chromatin condensation. In keeping with ultrastructural data, CdB-treated cells showed the typical flow cytometric hallmark of apoptosis consisting of a distinct sub-G, peak. The CdB-induced apoptotic response was dose and time dependent and not simply due to the actin-disrupting effect of the toxin or to the subsequent impairment of cell anchorage. Rather, the inhibition of proteins belonging to the Rho family due to CdB seems to play a role in the induction of apoptosis in intestinal cells. The origin of cells and the growth rate may also be cofactors relevant to such a response.