Osborne Suzanne E, Brumell John H
Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8
Philos Trans R Soc Lond B Biol Sci. 2017 Aug 5;372(1726). doi: 10.1098/rstb.2016.0222.
() is a Gram-positive facultative intracellular pathogen. Infections in humans can lead to listeriosis, a systemic disease with a high mortality rate. One important mechanism of dissemination involves cell-to-cell spread after bacteria have entered the cytosol of host cells. Listeriolysin O (LLO; encoded by the gene) is a virulence factor present in that plays a central role in the cell-to-cell spread process. LLO is a member of the cholesterol-dependent cytolysin (CDC) family of toxins that were initially thought to promote disease largely by inducing cell death and tissue destruction-essentially acting like a 'bazooka'. This view was supported by structural studies showing CDCs can form large pores in membranes. However, it is now appreciated that LLO has many subtle activities during infection of host cells, and many of these likely do not involve large pores, but rather small membrane perforations. It is also appreciated that membrane repair pathways of host cells play a major role in limiting membrane damage by LLO and other toxins. LLO is now thought to represent a 'Swiss army knife', a versatile tool that allows to induce many membrane alterations and cellular responses that promote bacterial dissemination during infection.This article is part of the themed issue 'Membrane pores: from structure and assembly, to medicine and technology'.
(某病原体)是一种革兰氏阳性兼性胞内病原体。人类感染该病原体可导致李斯特菌病,这是一种死亡率很高的全身性疾病。其传播的一个重要机制涉及细菌进入宿主细胞胞质溶胶后在细胞间的扩散。李斯特菌溶血素O(LLO;由特定基因编码)是该病原体中存在的一种毒力因子,在细胞间扩散过程中起核心作用。LLO是胆固醇依赖细胞毒素(CDC)家族毒素的成员,最初人们认为该家族毒素主要通过诱导细胞死亡和组织破坏来引发疾病——本质上就像一门“火箭炮”。结构研究表明CDC能在膜上形成大孔,这一观点得到了支持。然而,现在人们认识到LLO在感染宿主细胞过程中有许多微妙的活动,其中许多可能并不涉及大孔,而是小的膜穿孔。人们还认识到宿主细胞的膜修复途径在限制LLO和其他毒素造成的膜损伤方面起主要作用。现在认为LLO就像一把“瑞士军刀”,是一种多功能工具,使该病原体能够引发许多膜改变和细胞反应,从而在感染期间促进细菌传播。本文是主题为“膜孔:从结构与组装到医学与技术”的特刊的一部分。