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首页> 外文期刊>Infection and immunity >Identification of ElpA, a Coxiella burnetii Pathotype-Specific Dot/Icm Type IV Secretion System Substrate
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Identification of ElpA, a Coxiella burnetii Pathotype-Specific Dot/Icm Type IV Secretion System Substrate

机译：鉴定ElpA，伯氏柯氏杆菌病原体特异性Dot / Icm IV型分泌系统底物

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摘要

Coxiella burnetii causes human Q fever, a zoonotic disease that presents with acute flu-like symptoms and can result in chronic life-threatening endocarditis. In human alveolar macrophages, C. burnetii uses a Dot/Icm type IV secretion system (T4SS) to generate a phagolysosome-like parasitophorous vacuole (PV) in which to replicate. The T4SS translocates effector proteins, or substrates, into the host cytosol, where they mediate critical cellular events, including interaction with autophagosomes, PV formation, and prevention of apoptosis. Over 100 C. burnetii Dot/Icm substrates have been identified, but the function of most remains undefined. Here, we identified a novel Dot/Icm substrate-encoding open reading frame (CbuD1884) present in all C. burnetii isolates except the Nine Mile reference isolate, where the gene is disrupted by a frameshift mutation, resulting in a pseudogene. The CbuD1884 protein contains two transmembrane helices (TMHs) and a coiled-coil domain predicted to mediate protein-protein interactions. The C-terminal region of the protein contains a predicted Dot/Icm translocation signal and was secreted by the T4SS, while the N-terminal portion of the protein was not secreted. When ectopically expressed in eukaryotic cells, the TMH-containing N-terminal region of the CbuD1884 protein trafficked to the endoplasmic reticulum (ER), with the C terminus dispersed nonspecifically in the host cytoplasm. This new Dot/Icm substrate is now termed ElpA (ER-localizing protein A). Full-length ElpA triggered substantial disruption of ER structure and host cell secretory transport. These results suggest that ElpA is a pathotype-specific T4SS effector that influences ER function during C. burnetii infection.
机译：伯氏柯氏杆菌引起人Q发烧，这是一种人畜共患疾病，表现为急性流感样症状，并可能导致威胁生命的慢性心内膜炎。在人肺泡巨噬细胞中，伯氏梭状芽胞杆菌使用Dot / Icm IV型分泌系统（T4SS）产生吞噬体样的寄生虫空泡（PV），并在其中复制。 T4SS将效应蛋白或底物转移到宿主细胞质中，在其中介导关键的细胞事件，包括与自噬体的相互作用，PV的形成和细胞凋亡的预防。已经鉴定出超过100种伯氏梭菌Dot / Icm底物，但大多数功能仍不确定。在这里，我们确定了一个新颖的点/ Icm底物编码开放阅读框（CbuD1884），除了九英里参考分离株之外，所有伯氏梭菌分离株均存在，其中基因被移码突变破坏，产生假基因。 CbuD1884蛋白质包含两个跨膜螺旋（TMH）和一个预计会介导蛋白质-蛋白质相互作用的卷曲螺旋结构域。蛋白质的C末端区域包含一个预测的Dot / Icm易位信号，由T4SS分泌，而蛋白质的N末端部分则未被分泌。当在真核细胞中异位表达时，CbuD1884蛋白的含TMH的N末端区域转移到内质网（ER），C末端非特异性地分散在宿主细胞质中。现在将这种新的Dot / Icm底物称为ElpA（ER定位蛋白A）。全长ElpA触发了ER结构和宿主细胞分泌转运的实质性破坏。这些结果表明，ElpA是一种特定于病理类型的T4SS效应子，可在伯氏梭菌感染期间影响ER功能。

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