Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity.
Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity.
复制标题
DOI：
10.1111/j.1365-2958.2011.07905.x
复制
发表时间：
2011-12
影响因子：
3.6
通讯作者：
Han YW
中科院分区：
文献类型：
--
作者：
Fardini Y;Wang X;Témoin S;Nithianantham S;Lee D;Shoham M;Han YW
具核梭杆菌是一种革兰氏阴性的口腔厌氧菌，能够全身传播，引起感染和腹泻，通常是混合种，在不同的身体部位。我们以前已经证明，F。核质通过一种新的FadA粘附素粘附并侵入宿主上皮和内皮细胞。在这项研究中，血管内皮（VE）-钙粘蛋白，钙粘蛋白家族的成员和细胞间连接分子，被确定为FadA的内皮受体，需要F。有核物质与细胞结合。FadA与内皮细胞上的VE-钙粘蛋白共定位，导致VE-钙粘蛋白远离细胞-细胞连接的重新定位。结果，内皮通透性增加，允许细菌通过松弛的连接穿过内皮。这种穿越机制可以解释为什么生物体能够全身传播，在不同的身体部位定居，甚至克服胎盘和血脑屏障。F. nucleatum和E. coli在transwell实验中增强了后者对内皮细胞的穿透，提示F.有核质可以作为其他微生物全身传播的“使能物”。这可以解释为什么F。混合感染常出现有核细胞。这项研究揭示了病原体利用的一种可能的新传播机制。
Fusobacterium nucleatum is a gram-negative oral anaerobe, capable of systemic dissemination causing infections and abscesses, often in mixed-species, at different body sites. We have shown previously that F. nucleatum adheres to and invades host epithelial and endothelial cells via a novel FadA adhesin. In this study, vascular endothelial (VE)-cadherin, a member of the cadherin family and a cell-cell junction molecule, was identified as the endothelial receptor for FadA, required for F. nucleatum binding to the cells. FadA co-localized with VE-cadherin on endothelial cells, causing relocation of VE-cadherin away from the cell-cell junctions. As a result, the endothelial permeability was increased, allowing the bacteria to cross the endothelium through loosened junctions. This crossing mechanism may explain why the organism is able to disseminate systemically to colonize in different body sites and even overcome the placental and blood-brain barriers. Co-incubation of F. nucleatum and E. coli enhanced penetration of the endothelial cells by the latter in the transwell assays, suggesting F. nucleatum may serve as an “enabler” for other microorganisms to spread systemically. This may explain why F. nucleatum is often found in mixed infections. This study reveals a possible novel dissemination mechanism utilized by pathogens.
登录
查看更多内容
影响因子：
3
作者：
Kai, Anneke;Cooke, Fiona;Sule, Olajumoke
通讯作者：
Sule, Olajumoke
影响因子：
56.9
作者：
Coureuil, Mathieu;Mikaty, Guillain;Nassif, Xavier
通讯作者：
Nassif, Xavier
影响因子：
4.4
作者：
Liu, Hongqi;Redline, Raymond W.;Han, Yiping W.
通讯作者：
Han, Yiping W.
影响因子：
3.1
作者：
Han, YW;Shi, WY;Genco, RJ
通讯作者：
Genco, RJ
影响因子：
21.3
作者：
Kametani, Yoshiko;Takeichi, Masatoshi
通讯作者：
Takeichi, Masatoshi