Plasma membrane protrusions mediate host cell-cell fusion induced by Burkholderia thailandensis.
Plasma membrane protrusions mediate host cell-cell fusion induced by Burkholderia thailandensis.
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质膜突起介导泰兰伯克霍尔德氏菌诱导的宿主细胞-细胞融合。
DOI：
10.1091/mbc.e22-02-0056
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发表时间：
2022-07-01
影响因子：
3.3
通讯作者：
Welch, Matthew D.
中科院分区：
文献类型：
--
作者：
Kostow, Nora;Welch, Matthew D.
细胞-细胞融合对于包括受精、发育、免疫和微生物致病在内的生物过程是重要的。伯克霍尔德氏菌属类鼻疽菌群中的细菌，包括B。thailandensis，通过诱导细胞-细胞融合在宿主细胞之间传播。以前的工作表明，B. thailandensis诱导的细胞-细胞融合需要细胞内细菌运动性和称为VI型分泌系统-5（T6 SS-5）的细菌蛋白分泌装置，包括T6 SS-5蛋白VgrG 5。然而，细胞水平的机制和T6 SS-5蛋白的细菌诱导的细胞-细胞融合的重要性仍然不完全描述。使用活细胞成像，我们发现细菌使用基于肌动蛋白的运动来推动宿主细胞质膜，以形成延伸到邻近细胞的质膜突起。然后，膜融合发生在膜突起内，或者在尖端处接近细菌，或者在突起内的其他地方。VgrG 5在膜突起内由细菌表达是促进细胞-细胞融合所必需的。此外，第二个预测的T6 SS-5蛋白，TagD 5，也需要细胞-细胞融合。在缺乏VgrG 5或TagD 5的情况下，质膜突起中的细菌被吞噬到邻近的细胞中。我们的研究结果表明，T6 SS-5效应VgrG 5和TagD 5分泌膜突起内，并发挥局部作用，以促进膜融合。
Cell–cell fusion is important for biological processes including fertilization, development, immunity, and microbial pathogenesis. Bacteria in the pseudomallei group of the Burkholderia species, including B. thailandensis, spread between host cells by inducing cell–cell fusion. Previous work showed that B. thailandensis-induced cell–cell fusion requires intracellular bacterial motility and a bacterial protein secretion apparatus called the type VI secretion system-5 (T6SS-5), including the T6SS-5 protein VgrG5. However, the cellular-level mechanism of and T6SS-5 proteins important for bacteria-induced cell–cell fusion remained incompletely described. Using live-cell imaging, we found bacteria used actin-based motility to push on the host cell plasma membrane to form plasma membrane protrusions that extended into neighboring cells. Then, membrane fusion occurred within membrane protrusions either proximal to the bacterium at the tip or elsewhere within protrusions. Expression of VgrG5 by bacteria within membrane protrusions was required to promote cell–cell fusion. Furthermore, a second predicted T6SS-5 protein, TagD5, was also required for cell–cell fusion. In the absence of VgrG5 or TagD5, bacteria in plasma membrane protrusions were engulfed into neighboring cells. Our results suggest that the T6SS-5 effectors VgrG5 and TagD5 are secreted within membrane protrusions and act locally to promote membrane fusion.