The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state.
The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state.
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DOI：
10.1038/s41467-022-31176-9
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发表时间：
2022-06-23
影响因子：
16.6
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中科院分区：
文献类型：
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恙虫病东方体（Ot）是立克次体科中的一种专性细胞内细菌，可引起恙虫病，一种严重的螨传播的人类疾病。它的细胞退出机制在立克次体科中是不寻常的，因为Ot从被质膜包裹的感染细胞表面出芽。在这里，我们表明，Ot的细菌已经出芽出宿主细胞是在一个不同的发展阶段相比，细胞内的细菌。我们将这两个阶段称为细胞内和细胞外细菌（分别为IB和EB）。这两种形式在物理性质上不同：IB是圆形和细长的，而EB是圆形的。此外，与EB相比，IB具有更高水平的肽聚糖，并且在物理上是稳健的。这两种细菌形式差异表达参与细菌生理学和宿主-病原体相互作用的蛋白质，特别是参与细菌休眠和应激反应的蛋白质，以及外膜自转运蛋白ScaA和ScaC。虽然两个群体都是感染性的，但IB Ot的进入对网格蛋白介导的内吞作用和巨胞饮作用的抑制剂敏感，而EB Ot的进入仅对巨胞饮作用抑制剂敏感。我们的鉴定和详细表征的两种发展形式的Ot显着推进我们的细胞内生命周期的一个重要的人类病原体的理解。恙虫病东方体（Ot）是恙虫病的病原体，它通过一种独特的机制从受感染的细胞表面出芽。在这里，Atwal等人报告说，从其宿主细胞出芽的Ots处于与细胞内细菌不同的发育阶段，并提供了该细胞外阶段的第一个表征。这两种形式都是感染性的，但在它们的物理性质、蛋白质组和进入宿主细胞的机制上不同。
Orientia tsutsugamushi (Ot) is an obligate intracellular bacterium in the family Rickettsiaceae that causes scrub typhus, a severe mite-borne human disease. Its mechanism of cell exit is unusual amongst Rickettsiaceae, as Ot buds off the surface of infected cells enveloped in plasma membrane. Here, we show that Ot bacteria that have budded out of host cells are in a distinct developmental stage compared with intracellular bacteria. We refer to these two stages as intracellular and extracellular bacteria (IB and EB, respectively). These two forms differ in physical properties: IB is both round and elongated, and EB is round. Additionally, IB has higher levels of peptidoglycan and is physically robust compared with EB. The two bacterial forms differentially express proteins involved in bacterial physiology and host-pathogen interactions, specifically those involved in bacterial dormancy and stress response, and outer membrane autotransporter proteins ScaA and ScaC. Whilst both populations are infectious, entry of IB Ot is sensitive to inhibitors of both clathrin-mediated endocytosis and macropinocytosis, whereas entry of EB Ot is only sensitive to a macropinocytosis inhibitor. Our identification and detailed characterization of two developmental forms of Ot significantly advances our understanding of the intracellular lifecycle of an important human pathogen. Orientia tsutsugamushi (Ot) the causing agent of scrub typhus exits infected cells using a unique mechanism that involves budding off the surface of infected cells. Here, Atwal et al. report that Ots that have budded from their host cells are in a distinct developmental stage than intracellular bacteria and provide the first characterization of this extracellular stage. Both forms are infectious but differ in their physical properties, proteome, and entry mechanism into host cells.
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影响因子：
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作者：
Min CK;Yang JS;Kim S;Choi MS;Kim IS;Cho NH
通讯作者：
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影响因子：
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通讯作者：
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影响因子：
3.1
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通讯作者：
Kim, Ik-Sang
影响因子：
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作者：
HANSON, B
通讯作者：
HANSON, B