Department of Microbiology and Physiological Systems, University of Massachusetts Medical School Worcester, MA, USA.
Front Microbiol. 2011 Nov 8;2:222. doi: 10.3389/fmicb.2011.00222. eCollection 2011.
A member of the attaching and effacing (AE) family of pathogens, enterohemorrhagic Escherichia coli (EHEC) induces dramatic changes to the intestinal cell cytoskeleton, including effacement of microvilli. Effacement by the related pathogen enteropathogenic E. coli (EPEC) requires the activity of the Ca(+2)-dependent host protease, calpain, which participates in a variety of cellular processes, including cell adhesion and motility. We found that EHEC infection results in an increase in epithelial (CaCo-2a) cell calpain activity and that EHEC-induced microvillar effacement was blocked by ectopic expression of calpastatin, an endogenous calpain inhibitor, or by pretreatment of intestinal cells with a cell-penetrating version of calpastatin. In addition, ezrin, a known calpain substrate that links the plasma membrane to axial actin filaments in microvilli, was cleaved in a calpain-dependent manner during EHEC infection and lost from its normal locale within microvilli. Calpain may be a central conduit through which EHEC and other AE pathogens induce enterocyte cytoskeletal remodeling and exert their pathogenic effects.
附着和消除（AE）病原体家族的成员，肠出血性大肠杆菌（EHEC）引起肠道细胞骨架的剧烈变化，包括微绒毛的消除。相关病原体肠致病性大肠杆菌（EPEC）的消除需要 Ca(+2)-依赖性宿主蛋白酶，钙蛋白酶的活性，钙蛋白酶参与多种细胞过程，包括细胞粘附和运动。我们发现 EHEC 感染导致上皮（CaCo-2a）细胞钙蛋白酶活性增加，并且 EHEC 诱导的微绒毛消除被钙蛋白酶抑制剂 calpastatin 的异位表达或用穿透细胞的 calpastatin 预处理肠道细胞所阻断。此外，ezrin，一种已知的将质膜与微绒毛中轴向肌动蛋白丝连接的钙蛋白酶底物，在 EHEC 感染过程中以钙蛋白酶依赖性方式被切割，并从微绒毛中的正常位置丢失。钙蛋白酶可能是 EHEC 和其他 AE 病原体诱导肠细胞骨架重塑并发挥其致病作用的中心途径。
