Wbm0076, a candidate effector protein of the Wolbachia endosymbiont of Brugia malayi, disrupts eukaryotic actin dynamics.
Wbm0076, a candidate effector protein of the Wolbachia endosymbiont of Brugia malayi, disrupts eukaryotic actin dynamics.
复制标题
DOI：
10.1371/journal.ppat.1010777
复制
发表时间：
2023-02
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
马来丝虫是人类的一种寄生蛔虫，由专性细胞内细菌Wolbachia pipientis定殖。这种线虫和细菌之间的共生关系是线虫繁殖和在人类宿主中长期生存所必需的。因此，确定沃尔巴克氏体在B中持续存在和定殖所需的分子机制。马来人的组织将提供关于这种内共生的基本生物学的新的重要信息。沃尔巴克氏体利用IV型分泌系统将所谓的“效应”蛋白质转运到B的胞质溶胶中。malayi细胞以促进真核宿主的定殖。然而，这些沃尔巴克氏体分泌蛋白的表征仍然难以捉摸，由于这两种生物体的遗传棘手性。引人注目的是，候选Wolbachia IV型分泌的效应蛋白，Wbm 0076，在替代真核细胞模型，酿酒酵母，导致酵母肌动蛋白细胞骨架的破坏和抑制内吞作用的表达。遗传分析表明，Wbm 0076是Wiskott-Aldrich综合征蛋白（WAS [p]）家族的成员，WAS [p]是肌动蛋白骨架结构组织所需的高度保守的真核蛋白家族。因此，Wbm 0076可能在沃尔巴克氏体在整个B中的活跃细胞间运动中起核心作用。马来组织在线虫发育过程中。由于大多数沃尔巴克氏体菌株测序日期编码至少部分wBm 0076的直系同源物，我们发现很可能沃尔巴克氏体直接操纵宿主肌动蛋白动力学的能力是所有沃尔巴克氏体内共生的基本要求，独立于宿主细胞物种。盘尾丝虫科（Onchocerediae）的丝状线虫引起几种使人衰弱的疾病，例如淋巴丝虫病和盘尾丝虫病;在大多数热带和亚热带地区，超过5000万人感染这些节肢动物传播的蛔虫。许多这些线虫，包括马来丝虫，专性定殖由沃尔巴克氏体属的细胞内细菌，这是绝对需要的这些蠕虫在哺乳动物宿主中的正常发育和繁殖。从这些线虫中清除沃尔巴克氏体会导致蠕虫生存能力及其在人类中引起疾病的能力的丧失。然而，由于这些生物体的遗传难治性，理解维持这种重要的细菌：线虫内共生所需的分子相互作用的努力受到了阻碍。在这项工作中，我们利用酵母作为替代真核细胞显示，候选人分泌的效应蛋白从沃尔巴克氏体，Wbm 0076，破坏真核细胞肌动蛋白动力学和内吞作用。我们还观察到Wbm 0076与高度保守的真核细胞肌动蛋白调节蛋白的相互作用。由于一些细胞内的细菌操纵宿主肌动蛋白的动力学，以促进流动性内或进入宿主细胞，我们的研究提供了一个重要的沃尔巴克氏体蛋白的活性，可能是必不可少的适当的本地化过程中的B的发展的证据。马来语。
Brugia malayi, a parasitic roundworm of humans, is colonized by the obligate intracellular bacterium, Wolbachia pipientis. The symbiosis between this nematode and bacterium is essential for nematode reproduction and long-term survival in a human host. Therefore, identifying molecular mechanisms required by Wolbachia to persist in and colonize B. malayi tissues will provide new essential information regarding the basic biology of this endosymbiosis. Wolbachia utilize a Type IV secretion system to translocate so-called “effector” proteins into the cytosol of B. malayi cells to promote colonization of the eukaryotic host. However, the characterization of these Wolbachia secreted proteins has remained elusive due to the genetic intractability of both organisms. Strikingly, expression of the candidate Wolbachia Type IV-secreted effector protein, Wbm0076, in the surrogate eukaryotic cell model, Saccharomyces cerevisiae, resulted in the disruption of the yeast actin cytoskeleton and inhibition of endocytosis. Genetic analyses show that Wbm0076 is a member of the family of Wiskott-Aldrich syndrome proteins (WAS [p]), a well-conserved eukaryotic protein family required for the organization of actin skeletal structures. Thus, Wbm0076 likely plays a central role in the active cell-to-cell movement of Wolbachia throughout B. malayi tissues during nematode development. As most Wolbachia isolates sequenced to date encode at least partial orthologs of wBm0076, we find it likely that the ability of Wolbachia to directly manipulate host actin dynamics is an essential requirement of all Wolbachia endosymbioses, independent of host cell species. Filarial nematodes of the family Onchocercidae cause several debilitating human diseases such as lymphatic filariasis and onchocerciasis; more than 50 million people are infected by these arthropod-borne roundworms in mostly tropical and sub-tropical regions. Many of these nematodes, including Brugia malayi, are obligately colonized by an intracellular bacterium of the genus Wolbachia, which is absolutely required for the proper development and reproduction of these worms in a mammalian host. Clearance of Wolbachia from these nematodes leads to a loss of both worm viability and its ability to cause disease in humans. Efforts to understand the molecular interactions required to maintain this important bacterium: nematode endosymbiosis, however, have been hampered due to the genetic intractability of these organisms. In this work, we utilize yeast as a surrogate eukaryotic cell to show that a candidate secreted effector protein from Wolbachia, Wbm0076, disrupts eukaryotic actin dynamics and endocytosis. We also observe interactions of Wbm0076 with a highly-conserved eukaryotic actin regulatory protein. As some intracellular bacteria manipulate host actin dynamics to promote mobility within or into host cells, our study provides evidence of an important Wolbachia protein activity that may be essential for its proper localization during the development of B. malayi.
登录
查看更多内容
影响因子：
5.6
作者：
Feyder S;De Craene JO;Bär S;Bertazzi DL;Friant S
通讯作者：
Friant S
影响因子：
4.8
作者：
Fazi, B;Cope, MJTV;Castagnoli, L
通讯作者：
Castagnoli, L
影响因子：
3.3
作者：
Dewar, H;Warren, DT;Ayscough, KR
通讯作者：
Ayscough, KR
影响因子：
3.7
作者：
Carpinone EM;Li Z;Mills MK;Foltz C;Brannon ER;Carlow CKS;Starai VJ
通讯作者：
Starai VJ
DOI：
10.1016/j.bbalip.2019.03.007
发表时间：
2019-07-01
影响因子：
4.8
作者：
Degreif，Daniel;Cucu，Bayram;Bertl，Adam
通讯作者：
Bertl，Adam