Salmonella trafficking is defined by continuous dynamic interactions with the endolysosomal system.
Salmonella trafficking is defined by continuous dynamic interactions with the endolysosomal system.
复制标题
沙门氏菌的运输是通过与内溶血系统的连续动态相互作用来定义的。
DOI：
10.1111/j.1600-0854.2006.00529.x
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发表时间：
2007-03
期刊：
影响因子：
4.5
通讯作者：
Steele-Mortimer, Olivia
中科院分区：
文献类型：
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作者：
Drecktrah, Dan;Knodler, Leigh A;Howe, Dale;Steele-Mortimer, Olivia
侵入非吞噬宿主细胞后，肠沙门氏菌在称为含沙门氏菌液泡 (SCV) 的吞噬体样区室中存活并复制。现在已经确定，SCV 生物发生与吞噬体生物发生一样，涉及与内吞途径的连续相互作用。然而，沙门氏菌被认为可以限制这些相互作用，特别是避免末端溶酶体与 SCV 的融合。在这项研究中，我们使用高分辨率活细胞成像方法重新评估了这一过程，发现 SCV 和内吞途径之间存在意想不到的相互作用水平。直接相互作用，即晚期内体/溶酶体内容物转移至 SCV，在入侵后 30 分钟内检测到，并持续数小时。从机制上讲，这些相互作用与吞噬体-溶酶体融合非常相似，因为它们伴随着 SCV 的快速酸化，可以通过微管的化学扰动或液泡酸化来阻断，并且涉及小 GTPase Rab7。与含有内化大肠杆菌或热灭活沙门氏菌的液泡相比，SCV 确实表现出一定的融合和酸化延迟，尽管这似乎与任一 III 型分泌系统无关。这些结果提供了令人信服的证据，表明抑制 SCV-溶酶体融合并不是沙门氏菌在上皮细胞中建立复制生态位的主要决定因素。
Following invasion of non-phagocytic host cells, Salmonella enterica survives and replicates within a phagosome-like compartment known as the Salmonella-containing vacuole (SCV). It is now well established that SCV biogenesis, like phagosome biogenesis, involves sequential interactions with the endocytic pathway. However, Salmonella is believed to limit these interactions and, in particular, to avoid fusion of terminal lysosomes with the SCV. In this study, we reassessed this process using a high-resolution live-cell imaging approach and found an unanticipated level of interaction between the SCV and the endocytic pathway. Direct interactions, in which late endosomal/lysosomal content was transferred to SCVs, were detected within 30 min of invasion and continued for several hours. Mechanistically, these interactions were very similar to phagosome–lysosome fusion because they were accompanied by rapid acidification of the SCV, could be blocked by chemical perturbation of microtubules or vacuolar acidification and involved the small GTPase Rab7. In comparison with vacuoles containing internalized Escherichia coli or heat-killed Salmonella, SCVs did show some delay of fusion and acidification, although, this appeared to be independent of either type III secretion system. These results provide compelling evidence that inhibition of SCV–lysosome fusion is not the major determinant in establishment of the Salmonella replicative niche in epithelial cells.