A Brucella effector modulates the Arf6-Rab8a GTPase cascade to promote intravacuolar replication.
A Brucella effector modulates the Arf6-Rab8a GTPase cascade to promote intravacuolar replication.
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DOI：
10.15252/embj.2021107664
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发表时间：
2021-10-01
期刊：
影响因子：
--
通讯作者：
Celli J
中科院分区：
文献类型：
--
作者：
Borghesan E;Smith EP;Myeni S;Binder K;Knodler LA;Celli J
宿主细胞膜运输途径的重塑是许多细胞内微生物的共同致病特征，对它们的液泡内生命周期和增殖是必不可少的。流产布鲁氏菌通过VIRBIV型分泌系统介导的效应蛋白的传递，产生宿主内质网衍生的空泡(RBCV)，支持其细胞内的生长，其功能和作用方式大多尚不清楚。在这里，我们表明，效应器BspF通过干扰跨高尔基网络(TGN)和循环内细胞室之间的囊泡运输，特异性地促进布鲁氏菌在rBCV中的复制。BspF靶向循环内小体，抑制向TGN的逆行运输，并与Arf6 GTPase激活蛋白(GAP)ACAP1相互作用，扰乱循环内小体内依赖Arf6/Rab8a的运输，导致rBCV增加TGN相关囊泡，促进细菌生长。总之，这些发现为细菌调节膜运输提供了机械性的见解，膜运输用于促进细菌在细胞内空泡内的增殖。流产布鲁氏菌效应蛋白BspF与宿主GTPase激活蛋白ACAP1结合，通过减少泡向跨高尔基网络的逆行运输，促进细胞内细菌的生长。
Remodeling of host cellular membrane transport pathways is a common pathogenic trait of many intracellular microbes that is essential to their intravacuolar life cycle and proliferation. The bacterium Brucella abortus generates a host endoplasmic reticulum‐derived vacuole (rBCV) that supports its intracellular growth, via VirB Type IV secretion system‐mediated delivery of effector proteins, whose functions and mode of action are mostly unknown. Here, we show that the effector BspF specifically promotes Brucella replication within rBCVs by interfering with vesicular transport between the trans‐Golgi network (TGN) and recycling endocytic compartment. BspF targeted the recycling endosome, inhibited retrograde traffic to the TGN, and interacted with the Arf6 GTPase‐activating Protein (GAP) ACAP1 to dysregulate Arf6‐/Rab8a‐dependent transport within the recycling endosome, which resulted in accretion of TGN‐associated vesicles by rBCVs and enhanced bacterial growth. Altogether, these findings provide mechanistic insight into bacterial modulation of membrane transport used to promote their own proliferation within intracellular vacuoles. Brucella abortus effector protein BspF binding to host GTPase‐activating protein ACAP1 facilitates intracellular bacterial growth by decreasing retrograde vesicular transport to the trans‐Golgi network.
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