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The Dot/Icm Effector SdhA Is Necessary for Virulence of Legionella pneumophila in Galleria mellonella and A/J Mice

机译:点/ Icm效应子SdhA是马尼拉回廊和A / J小鼠中嗜肺军团杆菌毒力所必需的

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Legionella pneumophila is an intracellular bacterium that resides within amoebae and macrophages in a specialized compartment termed the Legionella-containing vacuole (LCV). As well as providing an intracellular niche for replication, the LCV helps to prevent the release of bacterial components into the cytoplasm. Recognition of these components as danger signals by the host activates immune responses leading to clearance of the bacterium. Here, we examined the role of two important virulence factors of L. pneumophila, the potent danger signal flagellin and the translocated Dot/Icm type IVB secretion system effector SdhA, which is crucial to maintain LCV integrity, in the Galleria mellonella infection model. We demonstrate that flagellin expression does not contribute to virulence, replication, or induction of clearance mechanisms. Conversely, SdhA expression is important for virulence. We found that in the absence of SdhA, the LCV in hemocytes showed signs of instability and leakage. Furthermore, in contrast to wild-type L. pneumophila, a ΔsdhA mutant caused a transient depletion of hemocytes and reduced mortality. Analysis of the ΔsdhA mutant in the A/J mouse model also showed a significant replication defect. Together, our data underline the crucial importance of SdhA in infection across different model organisms.
机译:嗜肺军团菌是一种细胞内细菌,它位于变形虫和巨噬细胞内,被称为“含军团菌的液泡”(LCV)。除了提供复制的细胞内生态位外,LCV还有助于防止细菌成分释放到细胞质中。宿主将这些成分识别为危险信号会激活导致细菌清除的免疫反应。在这里,我们检查了肺炎链球菌的两个重要毒力因子,即有效的危险信号鞭毛蛋白和易位的Dot / Icm型IVB分泌系统效应物SdhA(在保持梅勒菌感染模型中对维持LCV完整性至关重要的作用)的作用。我们证明鞭毛蛋白的表达不有助于毒性,复制或清除机制的诱导。相反,SdhA表达对于毒力很重要。我们发现,在没有SdhA的情况下,血细胞中的LCV表现出不稳定和渗漏的迹象。此外,与野生型肺炎支原体相反,Δ sdhA 突变体导致血细胞瞬时耗竭并降低了死亡率。 A / J小鼠模型中Δ sdhA 突变体的分析也显示出明显的复制缺陷。总之,我们的数据强调了SdhA在不同模型生物感染中的至关重要性。

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