Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, 92093-0322, USA.
Cell Host Microbe. 2011 Feb 17;9(2):147-57. doi: 10.1016/j.chom.2011.01.005.
Pore-forming toxins (PFTs) secreted by pathogenic bacteria are the most common bacterial protein toxins and are important virulence factors for infection. PFTs punch holes in host cell plasma membranes, and although cells can counteract the resulting membrane damage, the underlying mechanisms at play remain unclear. Using Caenorhabditis elegans as a model, we demonstrate in vivo and in an intact epithelium that intestinal cells respond to PFTs by increasing levels of endocytosis, dependent upon RAB-5 and RAB-11, which are master regulators of endocytic and exocytic events. Furthermore, we find that RAB-5 and RAB-11 are required for protection against PFT and to restore integrity to the plasma membrane. One physical mechanism involved is the RAB-11-dependent expulsion of microvilli from the apical side of the intestinal epithelial cells. Specific vesicle-trafficking pathways thus protect cells against an attack by PFTs on plasma membrane integrity, via altered plasma membrane dynamics.
孔形成毒素（PFTs）是由致病菌分泌的最常见的细菌蛋白毒素，也是感染的重要毒力因子。PFTs 在宿主细胞膜上打孔，尽管细胞可以对抗由此产生的膜损伤，但其中的作用机制仍不清楚。我们使用秀丽隐杆线虫作为模型，在体内和完整的上皮组织中证明，肠道细胞通过增加内吞作用来应对 PFTs，这依赖于 RAB-5 和 RAB-11，它们是内吞作用和外排作用的主要调节因子。此外，我们发现 RAB-5 和 RAB-11 对于抵抗 PFT 和恢复质膜完整性是必需的。所涉及的一种物理机制是 RAB-11 依赖性将微绒毛从肠上皮细胞的顶端侧驱逐。因此，通过改变质膜动力学，特定的囊泡运输途径可以保护细胞免受 PFT 对质膜完整性的攻击。
