Identification of cytokeratins as accessory mediators of Salmonella entry into eukaryotic cells

Identification of cytokeratins as accessory mediators of Salmonella entry into eukaryotic cells
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DOI:
10.1016/s0024-3205(01)01512-0
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发表时间:
2002-02-08
期刊:
影响因子:
6.1
通讯作者:
Jones, BD
Jones, BD
中科院分区:
医学2区
文献类型:
--
作者:
Carlson, SA;Omary, MB;Jones, BD

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致病性沙门氏菌通过诱导其自身被肠道M细胞摄取来启动哺乳动物宿主的感染。在摄取过程中,细菌利用内在分泌系统释放蛋白质进入宿主细胞。分泌的侵入介导蛋白随后与宿主细胞组分相互作用,诱导肌动蛋白细胞骨架的改变。为了确定潜在的细胞入侵的决定因素,我们采用酵母双杂交系统使用分泌沙门氏菌入侵蛋白(SipC)作为诱饵蛋白。该系统确定了细胞角蛋白,细胞骨架基质的支持性成分,作为可能与SipC物理相互作用的蛋白质。基于转染的研究显示,沙门氏菌的入侵时,显性负角蛋白-18的表达抑制。免疫荧光共聚焦显微镜研究表明,沙门氏菌没有进入HEp-2细胞表达显性阴性角蛋白-18。这些结果表明,SipC和细胞角蛋白-18之间的相互作用可能会发生沙门氏菌入侵的一部分。(C)2002年爱思唯尔科技有限公司All rights reserved.
Pathogenic Salmonella species initiate infection of a mammalian host by inducing their own uptake into intestinal M-cells. During the uptake process, the bacteria utilize an intrinsic secretion system to release proteins that enter host cells. The secreted invasion-mediating proteins subsequently interact with host cell components that induce alterations in the actin cytoskeleton. To identify potential cellular determinants of invasion, we employed a yeast two-hybrid system using the secreted Salmonella invasion protein (SipC) as the bait protein. This system identified cytokeratins, supportive components of the cytoskeletal matrix, as proteins that may physically interact with SipC. Transfection-based studies revealed an inhibition of Salmonella invasion when a dominant negative cytokeratin-18 was expressed. Immunofluorescent confocal microscopy studies revealed that Salmonella did not enter HEp-2 cells expressing the dominant negative cytokeratin-18. These results suggest that an interaction between SipC and cytokeratin-18 may occur as part of Salmonella invasion. (C) 2002 Elsevier Science Inc. All rights reserved.