Recruitment of the major vault protein by InlK: a Listeria monocytogenes strategy to avoid autophagy.
Recruitment of the major vault protein by InlK: a Listeria monocytogenes strategy to avoid autophagy.
复制标题
DOI：
10.1371/journal.ppat.1002168
复制
发表时间：
2011-08
期刊：
影响因子：
6.7
通讯作者：
Cossart P
中科院分区：
文献类型：
--
作者：
Dortet L;Mostowy S;Samba-Louaka A;Gouin E;Nahori MA;Wiemer EA;Dussurget O;Cossart P
单核增生乳杆菌是李斯特菌病的兼性细胞内细菌。它能在吞噬细胞和非吞噬细胞中侵入、存活和复制。细胞水平的感染过程已被广泛研究，许多毒力因子已被确定。然而，作为单核增生乳杆菌特有的内毒素家族成员，InlK的作用尚不清楚。这里,我们首先显示使用删除分析和体内感染,InlK是善意的毒力因子,体外和体内表达,不善表达,它是固定在细菌表面由sortase a .然后我们演示两个混合酵母屏幕使用InlK作为诱饵,验证了下拉实验和免疫荧光分析intracytosolic细菌通过与蛋白质InlK与主要的库(MVP),细胞质核糖核蛋白微粒的主要成分称为穹窿。尽管穹窿与几个细胞过程有关，但它们的作用仍然难以捉摸。我们的分析表明，MVP的募集掩盖了胞浆内细菌的自噬识别，导致与InlK -细菌相比，InlK过表达细菌的存活率增加。总之，这些结果表明，MVP被单核细胞增生乳杆菌劫持，以抵消自噬过程，这一发现可能对破译拱顶颗粒的细胞作用具有重要意义。李斯特菌病是一种致死率高的严重疾病，主要影响免疫功能低下的患者和孕妇。这种细菌是一种兼性细胞内病原体，能够在多种细胞中侵入、存活和繁殖。尽管在细胞水平上的感染过程已被广泛研究，但单核增生乳杆菌特异性表面蛋白InlK的作用仍不清楚。本研究发现，单核增生乳杆菌利用InlK与哺乳动物细胞质蛋白主要拱顶蛋白（MVP）相互作用。尽管MVP与多种细胞过程有关，但其作用仍然难以捉摸。在这里，我们证明了在细胞内，单核增生乳杆菌能够通过InlK用MVP装饰其表面以逃避自噬，这是一种保护细胞免受病原体入侵的先天免疫防御系统。单核增生乳杆菌利用这种伪装策略有效地在细胞内生存。
L. monocytogenes is a facultative intracellular bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The infectious process at the cellular level has been extensively studied and many virulence factors have been identified. Yet, the role of InlK, a member of the internalin family specific to L. monocytogenes, remains unknown. Here, we first show using deletion analysis and in vivo infection, that InlK is a bona fide virulence factor, poorly expressed in vitro and well expressed in vivo, and that it is anchored to the bacterial surface by sortase A. We then demonstrate by a yeast two hybrid screen using InlK as a bait, validated by pulldown experiments and immunofluorescence analysis that intracytosolic bacteria via an interaction with the protein InlK interact with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoproteic particules named vaults. Although vaults have been implicated in several cellular processes, their role has remained elusive. Our analysis demonstrates that MVP recruitment disguises intracytosolic bacteria from autophagic recognition, leading to an increased survival rate of InlK over-expressing bacteria compared to InlK− bacteria. Together these results reveal that MVP is hijacked by L. monocytogenes in order to counteract the autophagy process, a finding that could have major implications in deciphering the cellular role of vault particles. L. monocytogenes is a food-born pathogen responsible for listeriosis, a severe illness with a high mortality rate, which mainly affects immunocompromised patients and pregnant women. The bacterium is a facultative intracellular pathogen able to invade, survive and multiply in large variety of cells. Although the infectious process at the cellular level has been extensively studied, the role of InlK, a surface protein specific to L. monocytogenes, remains unknown. Here we established that L. monocytogenes use InlK to interact with a mammalian cytoplasmic protein named Major Vault Protein (MVP). Although MVP has been implicated in diverse cellular processes, its role remains elusive. Here we demonstrate that, inside the cell, L. monocytogenes is able, via InlK, to decorate its surface with MVP to escape autophagy, an innate immune defense system that protects the cell from invading pathogens. L. monocytogenes uses this camouflage strategy to efficiently survive inside cells.
登录
查看更多内容
影响因子：
2.9
作者：
Boujemaa-Paterski, R;Gouin, E;Pantaloni, D
通讯作者：
Pantaloni, D
影响因子：
3.4
作者：
Henry, R;Shaughnessy, L;Swanson, JA
通讯作者：
Swanson, JA
影响因子：
6.7
作者：
Camejo A;Buchrieser C;Couvé E;Carvalho F;Reis O;Ferreira P;Sousa S;Cossart P;Cabanes D
通讯作者：
Cabanes D
DOI：
10.1083/jcb.103.3.699
发表时间：
1986-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kedersha NL;Rome LH
通讯作者：
Rome LH
影响因子：
5.8
作者：
Bierne, H.;Sabet, C.;Cossart, R.
通讯作者：
Cossart, R.