Acevedo-Sánchez Yamilex, Woida Patrick J, Anderson Caroline, Kraemer Stephan, Lamason Rebecca L
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Microbiology Program, Massachusetts Institute of Technology , Cambridge, MA, USA.
J Cell Biol. 2025 Mar 3;224(3). doi: 10.1083/jcb.202406122. Epub 2025 Jan 7.
Upon invasion into the host cell, a subset of bacterial pathogens resides exclusively in the cytosol. While previous research revealed how they reshape the plasma membrane during invasion, subvert the immune response, and hijack cytoskeletal dynamics to promote their motility, it was unclear if these pathogens also interacted with the organelles in this crowded intracellular space. Here, we examined if the obligate intracellular pathogen Rickettsia parkeri interacts with the endoplasmic reticulum (ER), a large and dynamic organelle spread throughout the cell. Using live-cell microscopy and transmission and focused-ion-beam scanning electron microscopy, we show that R. parkeri forms extensive contacts with the rough ER that are ∼55 nm apart and cover more than half the bacterial surface. Depletion of the ER-specific tethers VAPA and VAPB reduced rickettsia-ER contacts, and VAPA and VAPB were localized around intracellular rickettsiae. Overall, our findings illuminate an interkingdom ER contact uniquely mediated by rickettsiae that mimics some characteristics of traditional host membrane contact sites.
侵入宿主细胞后，一部分细菌病原体仅存在于细胞质溶胶中。虽然先前的研究揭示了它们在入侵过程中如何重塑质膜、颠覆免疫反应以及劫持细胞骨架动力学以促进其运动，但尚不清楚这些病原体是否也在这个拥挤的细胞内空间中与细胞器相互作用。在这里，我们研究了专性细胞内病原体帕克立克次体是否与内质网（ER）相互作用，内质网是一种遍布整个细胞的大型动态细胞器。使用活细胞显微镜、透射电子显微镜和聚焦离子束扫描电子显微镜，我们发现帕克立克次体与糙面内质网形成广泛接触，间距约为55纳米，覆盖细菌表面一半以上。内质网特异性连接蛋白VAPA和VAPB的耗竭减少了立克次体与内质网的接触，并且VAPA和VAPB定位于细胞内立克次体周围。总体而言，我们的研究结果揭示了一种由立克次体独特介导的跨界内质网接触，它模仿了传统宿主膜接触位点的一些特征。
