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首页> 外文期刊>Infection and immunity >Cholesterol Depletion Reduces Entry of Campylobacter jejuni Cytolethal Distending Toxin and Attenuates Intoxication of Host Cells
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Cholesterol Depletion Reduces Entry of Campylobacter jejuni Cytolethal Distending Toxin and Attenuates Intoxication of Host Cells

机译：胆固醇消耗减少空肠弯曲菌细胞致死毒素的进入并减轻宿主细胞的中毒

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摘要

Campylobacter jejuni is a common cause of pediatric diarrhea worldwide. Cytolethal distending toxin, produced by Campylobacter jejuni, is a putative virulence factor that induces cell cycle arrest and apoptosis in eukaryotic cells. Cellular cholesterol, a major component of lipid rafts, has a pivotal role in regulating signaling transduction and protein trafficking as well as pathogen internalization. In this study, we demonstrated that cell intoxication by Campylobacter jejuni cytolethal distending toxin is through the association of cytolethal distending toxin subunits and membrane cholesterol-rich microdomains. Cytolethal distending toxin subunits cofractionated with detergent-resistant membranes, while the distribution reduced upon the depletion of cholesterol, suggesting that cytolethal distending toxin subunits are associated with lipid rafts. The disruption of cholesterol using methyl-β-cyclodextrin not only reduced the binding activity of cytolethal distending toxin subunits on the cell membrane but also impaired their delivery and attenuated toxin-induced cell cycle arrest. Accordingly, cell intoxication by cytolethal distending toxin was restored by cholesterol replenishment. These findings suggest that membrane cholesterol plays a critical role in the Campylobacter jejuni cytolethal distending toxin-induced pathogenesis of host cells.
机译：空肠弯曲杆菌是全世界小儿腹泻的常见原因。空肠弯曲杆菌产生的致死性细胞毒素是一种假定的致病因子，可诱导真核细胞的细胞周期停滞和凋亡。细胞胆固醇是脂质筏的主要组成部分，在调节信号转导和蛋白质运输以及病原体内在化方面具有关键作用。在这项研究中，我们证明了空肠弯曲杆菌细胞致死性扩张毒素的细胞中毒是通过细胞致死性扩张毒素亚基与富含胆固醇的微结构域的联系而实现的。细胞致死性扩展毒素亚基与耐洗涤剂膜共分离，而分布随着胆固醇的消耗而减少，这表明细胞致死性扩展毒素亚基与脂质筏相关。使用甲基-β-环糊精破坏胆固醇不仅降低了细胞膜上细胞致死性扩展毒素亚基的结合活性，而且损害了它们的传递并减弱了毒素诱导的细胞周期停滞。因此，通过补充胆固醇来恢复因细胞致死性膨胀毒素引起的细胞中毒。这些发现表明膜胆固醇在空肠弯曲杆菌细胞致死性扩张毒素诱导的宿主细胞发病中起关键作用。

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