Biozentrum, University of Basel, Spitalstrasse 41, 4056 Basel, Switzerland.
Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117596, Singapore.
Cell Host Microbe. 2024 May 8;32(5):676-692.e5. doi: 10.1016/j.chom.2024.03.013. Epub 2024 Apr 18.
To spread within a host, intracellular Burkholderia form actin tails to generate membrane protrusions into neighboring host cells and use type VI secretion system-5 (T6SS-5) to induce cell-cell fusions. Here, we show that B. thailandensis also uses T6SS-5 to lyse protrusions to directly spread from cell to cell. Dynamin-2 recruitment to the membrane near a bacterium was followed by a short burst of T6SS-5 activity. This resulted in the polymerization of the actin of the newly invaded host cell and disruption of the protrusion membrane. Most protrusion lysis events were dependent on dynamin activity, caused no cell-cell fusion, and failed to be recognized by galectin-3. T6SS-5 inactivation decreased protrusion lysis but increased galectin-3, LC3, and LAMP1 accumulation in host cells. Our results indicate that B. thailandensis specifically activates T6SS-5 assembly in membrane protrusions to disrupt host cell membranes and spread without alerting cellular responses, such as autophagy.
为了在宿主内传播，胞内伯克霍尔德菌形成肌动蛋白尾巴，在邻近的宿主细胞中产生膜突起，并利用六型分泌系统 5（T6SS-5）诱导细胞融合。在这里，我们表明，B. thailandensis 也利用 T6SS-5 裂解突起，直接在细胞间扩散。肌球蛋白 2 募集到靠近细菌的膜上，随后是 T6SS-5 活性的短暂爆发。这导致新入侵宿主细胞的肌动蛋白聚合，并破坏突起膜。大多数突起裂解事件依赖于肌球蛋白活性，不引起细胞-细胞融合，并且不能被半乳糖凝集素-3 识别。T6SS-5 失活减少了突起裂解，但增加了宿主细胞中半乳糖凝集素-3、LC3 和 LAMP1 的积累。我们的结果表明，B. thailandensis 专门在膜突起中激活 T6SS-5 组装，以破坏宿主细胞膜并扩散，而不会引起细胞反应，如自噬。
