science20121116-6

来自英国帝国理工学院的研究人员发现细菌性病原体沙门氏菌干扰宿主细胞防御机制的途径。沙门氏菌通过干扰甘露糖-6-磷酸受体(宿主细胞溶酶体酶靶定目标所需)的胞内运输,导致宿主细胞中的溶酶体丧失杀菌能力,随后沙门氏菌就会掠夺这些被缴械的溶酶体,从而干扰宿主细胞的免疫防御。

-2012年11月16日《科学》

中文翻译


【题目】沙门氏菌抑制甘露糖-6-磷酸受体的逆向运输和溶酶体功能

【译文】肠道沙门氏菌(Salmonella enterica)是一种胞内细菌性病原体,它能向宿主细胞注射一种效应蛋白,从而使得它能在膜结合的液泡内正常复制。沙门氏菌的液泡含有溶酶体,但甘露糖-6-磷酸受体(MPRs)负责转运的水解酶能够减少沙门氏菌的液泡数量。本研究发现效应蛋白SifA会破坏依赖Rab9的MPRs的逆向运输,导致溶酶体的杀菌能力减弱。这一过程需要结合到宿主细胞的SifA蛋白来靶定结合SKIP/PLEKHM2蛋白。此外,SKIP在正常细胞内负责调控MPRs的逆向运输。在被感染细胞内,易位的SifA蛋白与SKIP和Rab9形成稳定的复合物。SifA-SKIP能够隔离Rab9,这就解释了SifA蛋白对MPR的转运和溶酶体功能的效应。在溶酶体活性降低的细胞中,沙门氏菌的繁殖速率加快,而在溶酶体活性较高的细胞中,沙门氏菌的繁殖速率降低。这些结果表明沙门氏菌的SifA蛋白能够降低溶酶体的杀菌能力,然后它的液泡将溶酶体融合。

英文原稿


[Title]: Salmonella Inhibits Retrograde Trafficking of Mannose-6-Phosphate Receptors and Lysosome Function

[Authors]: Kieran McGourty, Teresa L. Thurston, Sophie A. Matthews, Laurie Pinaud, Luís Jaime Mota, and David W. Holden

[Abstract]: Salmonella enterica is an intracellular bacterial pathogen that replicates within membrane-bound vacuoles through the action of effector proteins translocated into host cells. Salmonella vacuoles have characteristics of lysosomes but are reduced in hydrolytic enzymes transported by mannose-6-phosphate receptors (MPRs). We found that the effector SifA subverted Rab9-dependent retrograde trafficking of MPRs, thereby attenuating lysosome function. This required binding of SifA to its host cell target SKIP/PLEKHM2. Furthermore, SKIP regulated retrograde trafficking of MPRs in noninfected cells. Translocated SifA formed a stable complex with SKIP and Rab9 in infected cells. Sequestration of Rab9 by SifA-SKIP accounted for the effect of SifA on MPR transport and lysosome function. Growth of Salmonella increased in cells with reduced lysosomal activity and decreased in cells with higher lysosomal activity. These results suggest that Salmonella vacuoles undergo fusion with lysosomes whose potency has been reduced by SifA.

原文地址

http://www.sciencemag.org/content/338/6109/963.short

 

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