The type 3 secretion effector IpgD promotes S. flexneri dissemination.
The type 3 secretion effector IpgD promotes S. flexneri dissemination.
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DOI：
10.1371/journal.ppat.1010324
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发表时间：
2022-03
期刊：
影响因子：
6.7
通讯作者：
Agaisse H
中科院分区：
文献类型：
--
作者：
Köseoğlu VK;Jones MK;Agaisse H
细菌性病原体福氏志贺菌每年在全世界引起2.7亿例细菌性痢疾，导致20多万人死亡。S.弗氏菌的致病特性依赖于其侵入上皮细胞和在结肠上皮内从细胞扩散到细胞的能力。这种传播过程依赖于感染细胞胞质溶胶中基于肌动蛋白的运动性和膜突起的形成，所述膜突起突出到相邻细胞中并分解成病原体从中逃逸的双膜空泡（DMV），从而实现细胞到细胞的传播。S. 3型分泌系统（T3 SS）通过知之甚少的机制促进弗氏菌传播。在这里，我们表明，T3 SS效应IpgD促进分辨率的膜突起到DMVs在S。弗氏传播。IpgD的磷脂酰肌醇4-磷酸酶活性降低膜突起中的PtdIns（4，5）P2水平，从而抵消突起中的从头皮质肌动蛋白形成，这是一个限制突起分解为DMV的过程。最后，使用婴儿兔志贺氏菌病模型，我们表明，IpgD是所需的有效的细胞间传播在体内，并有助于痢疾的严重程度。细胞内病原体福氏志贺菌是细菌性痢疾（便血）的病原体。上皮细胞的侵袭和细胞间的扩散是S.弗氏致病机理细胞间的扩散依赖于膜突起的形成，这些膜突起突出到相邻的细胞中并分解成空泡。支持这一传播过程的分子机制知之甚少。在这项研究中，我们表明，S。福氏杆菌利用T3 SS效应蛋白IpgD的磷脂酰肌醇磷酸酶活性来操纵突起膜中的磷酸肌醇。磷酸肌醇信号的操纵限制了突起膜下肌动蛋白网络的形成，否则这将阻止突起断裂成空泡。我们还表明，IpgD是所需的有效传播在结肠的婴儿兔，并有助于疾病的严重程度。这项研究阐明了细胞内病原体如何操纵磷酸肌醇信号支持细菌的发病机制。
The bacterial pathogen Shigella flexneri causes 270 million cases of bacillary dysentery worldwide every year, resulting in more than 200,000 deaths. S. flexneri pathogenic properties rely on its ability to invade epithelial cells and spread from cell to cell within the colonic epithelium. This dissemination process relies on actin-based motility in the cytosol of infected cells and formation of membrane protrusions that project into adjacent cells and resolve into double-membrane vacuoles (DMVs) from which the pathogen escapes, thereby achieving cell-to-cell spread. S. flexneri dissemination is facilitated by the type 3 secretion system (T3SS) through poorly understood mechanisms. Here, we show that the T3SS effector IpgD facilitates the resolution of membrane protrusions into DMVs during S. flexneri dissemination. The phosphatidylinositol 4-phosphatase activity of IpgD decreases PtdIns(4,5)P2 levels in membrane protrusions, thereby counteracting de novo cortical actin formation in protrusions, a process that restricts the resolution of protrusions into DMVs. Finally, using an infant rabbit model of shigellosis, we show that IpgD is required for efficient cell-to-cell spread in vivo and contributes to the severity of dysentery. The intracellular pathogen Shigella flexneri is the causative agent of bacillary dysentery (blood in stool). Invasion of epithelial cells and cell-to-cell spread are critical determinants of S. flexneri pathogenesis. Cell-to-cell spread relies on the formation of membrane protrusions that project into adjacent cells and resolve into vacuoles. The molecular mechanisms supporting this dissemination process are poorly understood. In this study, we show that S. flexneri employs the phosphatidylinositol phosphatase activity of the T3SS effector protein IpgD to manipulate phosphoinositides in the protrusion membrane. Manipulation of phosphoinositide signaling restricts the formation of actin networks underneath the protrusion membrane, which would otherwise prevent the scission of protrusions into vacuoles. We also demonstrate that IpgD is required for efficient dissemination in the colon of infant rabbits and contributes to the severity of disease. This study exemplifies how manipulation of phosphoinositide signaling by intracellular pathogens supports bacterial pathogenesis.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.7
作者：
Agaisse H
通讯作者：
Agaisse H
影响因子：
3.1
作者：
ALLAOUI, A;MENARD, R;PARSOT, C
通讯作者：
PARSOT, C
DOI：
10.1083/jcb.146.6.1319
发表时间：
1999-09-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Egile C;Loisel TP;Laurent V;Li R;Pantaloni D;Sansonetti PJ;Carlier MF
通讯作者：
Carlier MF
影响因子：
30.3
作者：
Campbell-Valois, Francois-Xavier;Schnupf, Pamela;Parsot, Claude
通讯作者：
Parsot, Claude