Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK; Department of Immunology & Infection, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
MICALIS, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas 78350, France.
Cell Host Microbe. 2018 Dec 12;24(6):866-874.e4. doi: 10.1016/j.chom.2018.11.005.
The cytoskeleton occupies a central role in cellular immunity by promoting bacterial sensing and antibacterial functions. Septins are cytoskeletal proteins implicated in various cellular processes, including cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella, yet how septins recognize bacteria is poorly understood. Here, we discover that septins are recruited to regions of micron-scale membrane curvature upon invasion and division by a variety of bacterial species. Cardiolipin, a curvature-specific phospholipid, promotes septin recruitment to highly curved membranes of Shigella, and bacterial mutants lacking cardiolipin exhibit less septin cage entrapment. Chemically inhibiting cell separation to prolong membrane curvature or reducing Shigella cell growth respectively increases and decreases septin cage formation. Once formed, septin cages inhibit Shigella cell division upon recruitment of autophagic and lysosomal machinery. Thus, recognition of dividing bacterial cells by the septin cytoskeleton is a powerful mechanism to restrict the proliferation of intracellular bacterial pathogens.
细胞骨架通过促进细菌感应和抗菌功能,在细胞免疫中占据核心地位。GTP 结合蛋白 septin 是一种细胞骨架蛋白,参与多种细胞过程,包括细胞分裂。GTP 结合蛋白 septin 也会组装成笼状结构,将胞质中的志贺氏菌困住,但 septin 如何识别细菌还知之甚少。在这里,我们发现 septin 在多种细菌入侵和分裂时被招募到微米级膜曲率区域。心磷脂是一种曲率特异性磷脂,可促进 septin 募集到志贺氏菌高度弯曲的膜上,缺乏心磷脂的细菌突变体显示出较少的 septin 笼捕获。化学抑制细胞分离以延长膜曲率或分别降低志贺氏菌细胞生长,会增加和减少 septin 笼的形成。一旦形成,septin 笼在招募自噬和溶酶体机制后会抑制志贺氏菌的细胞分裂。因此,septin 细胞骨架识别分裂的细菌细胞是限制细胞内细菌病原体增殖的一种强大机制。