Alteration of epithelial cell lysosomal integrity induced by bacterial cholesterol-dependent cytolysins.
Alteration of epithelial cell lysosomal integrity induced by bacterial cholesterol-dependent cytolysins.
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DOI：
10.1111/cmi.12682
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发表时间：
2017-04
影响因子：
3.4
通讯作者：
Ribet D
中科院分区：
文献类型：
--
作者：
Malet JK;Cossart P;Ribet D
细菌病原体可以在感染宿主细胞细胞器（例如线粒体、内质网-高尔基体系统或细胞核）期间干扰。由于重要的细胞功能通常被划分在这些细胞器中，因此它们的靶向允许病原体在感染期间操纵关键的宿主功能。在这里，我们将溶酶体确定为致病菌单核细胞增生李斯特氏菌靶向的一类新细胞器。我们证明，细胞外李斯特菌通过分泌成孔毒素李斯特菌溶血素 O，改变上皮细胞中的溶酶体完整性，但不会改变巨噬细胞中的溶酶体完整性。李斯特菌溶血素 O 诱导溶酶体膜通透并释放溶酶体内容物，例如组织蛋白酶，这些蛋白酶在宿主细胞质中保持短暂活性。我们还发现其他细菌成孔毒素，例如产气荚膜溶血素 O 和肺炎球菌溶血素，也会诱导溶酶体改变。总之，我们的数据揭示了细菌胆固醇依赖性溶细胞素的新活性。
Bacterial pathogens can interfere during infection with host cell organelles, such as mitochondria, the endoplasmic reticulum‐Golgi system or nuclei. As important cellular functions are often compartmentalized in these organelles, their targeting allows pathogens to manipulate key host functions during infection. Here, we identify lysosomes as a new class of organelles targeted by the pathogenic bacterium Listeria monocytogenes. We demonstrate that extracellular Listeria, via secretion of the pore‐forming toxin listeriolysin O, alters lysosomal integrity in epithelial cells but not in macrophages. Listeriolysin O induces lysosomal membrane permeabilization and release of lysosomal content, such as cathepsins proteases, which remain transiently active in the host cytosol. We furthermore show that other bacterial pore‐forming toxins, such as perfringolysin O and pneumolysin, also induce lysosomes alteration. Together, our data unveil a novel activity of bacterial cholesterol‐dependent cytolysins.