Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase.
Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase.
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DOI：
10.1080/15548627.2016.1217369
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发表时间：
2016-11
期刊：
影响因子：
13.3
通讯作者：
Rikihisa Y
中科院分区：
文献类型：
--
作者：
Lin M;Liu H;Xiong Q;Niu H;Cheng Z;Yamamoto A;Rikihisa Y
查菲埃立克体是一种专性细胞内细菌，可引起潜在致命的人畜共患病，即人单核细胞埃立克体病。E. Chaffeensis具有有限的生物合成和代谢能力，因此主要依赖于宿主合成的营养物来生长。虽然宿主细胞质中富含这些营养物质，如E. chaffeensis被限制在早期的内体样膜结合区室中，只有进入该区室的宿主营养物才能被该细菌利用。这是如何发生的是未知的。我们发现，埃里希体复制依赖于自噬诱导，涉及III类磷脂酰肌醇3-激酶（PtdIns 3 K）活性，BECN 1（Beclin 1）和ATG 5（自噬相关5）。埃里希体获得宿主细胞预掺入的氨基酸在III类PtdIns 3 K依赖的方式和埃里希体的生长增强治疗雷帕霉素，自噬诱导剂。此外，ATG 5和RAB 5A/B/C被引导至埃里希体包涵体。RAB 5A/B/C siRNA敲低、RAB 5特异性GTP酶激活蛋白或显性阴性RAB 5A的过表达抑制了埃立克体感染，表明GTP结合的RAB 5在感染过程中的关键作用。天然和异位表达的埃里希体IV型分泌效应蛋白Etf-1结合RAB 5和自噬起始III类PtdIns 3 K复合物PIK 3C 3/VPS 34和BECN 1，并归巢于埃里希体包涵体。异位表达的Etf-1激活III类PtdIns 3 K，如在E. chaffeensis感染和诱导自噬体形成，清除聚集倾向的突变亨廷顿蛋白在III类PtdIns 3 K依赖的方式，并增强埃里希体增殖。这些数据支持E. Chaffeensis分泌Etf-1以诱导自噬，从而通过RAB 5和III类PtdIns 3 K重新利用宿主细胞质并捕获营养物用于其生长，同时避免自体溶酶体杀伤。
Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as E. chaffeensis is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown. We found that ehrlichial replication depended on autophagy induction involving class III phosphatidylinositol 3-kinase (PtdIns3K) activity, BECN1 (Beclin 1), and ATG5 (autophagy-related 5). Ehrlichia acquired host cell preincorporated amino acids in a class III PtdIns3K-dependent manner and ehrlichial growth was enhanced by treatment with rapamycin, an autophagy inducer. Moreover, ATG5 and RAB5A/B/C were routed to ehrlichial inclusions. RAB5A/B/C siRNA knockdown, or overexpression of a RAB5-specific GTPase-activating protein or dominant-negative RAB5A inhibited ehrlichial infection, indicating the critical role of GTP-bound RAB5 during infection. Both native and ectopically expressed ehrlichial type IV secretion effector protein, Etf-1, bound RAB5 and the autophagy-initiating class III PtdIns3K complex, PIK3C3/VPS34, and BECN1, and homed to ehrlichial inclusions. Ectopically expressed Etf-1 activated class III PtdIns3K as in E. chaffeensis infection and induced autophagosome formation, cleared an aggregation-prone mutant huntingtin protein in a class III PtdIns3K-dependent manner, and enhanced ehrlichial proliferation. These data support the notion that E. chaffeensis secretes Etf-1 to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 and class III PtdIns3K, while avoiding autolysosomal killing.
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影响因子：
9.4
作者：
ANDERSON, BE;DAWSON, JE;WILSON, KH
通讯作者：
WILSON, KH
DOI：
10.1083/jcb.201403009
发表时间：
2014-07-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
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影响因子：
3.4
作者：
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影响因子：
4.9
作者：
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影响因子：
3.2
作者：
Bao, Weichao;Kumagai, Yumi;Rikihisa, Yasuko
通讯作者：
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