Host cell caveolae act as an entry-port for group A streptococci
Host cell caveolae act as an entry-port for group A streptococci
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DOI：
10.1046/j.1462-5822.2003.00279.x
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Talay, SR
中科院分区：
文献类型：
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作者：
Rohde, M;Müller, E;Talay, SR
本研究确定了小泡是A组链球菌进入上皮细胞和内皮细胞的入口。扫描电子显微镜以及感染细胞的超薄切片显示，宿主细胞膜上靠近黏附链球菌的地方积聚了小的欧米茄形空腔。在侵袭过程中，内陷形成，随后发现围绕链球菌的细胞内腔室。小窝蛋白-1存在于内陷膜和室膜中。这些隔室缺乏任何典型的内体/溶酶体标记蛋白，因此可以被描述为腔体。甲基- β -环糊精和filipin破坏小泡可阻止宿主细胞入侵。重要的是，洞体内的链球菌避免与溶酶体融合。SfbI蛋白在非侵袭性金黄色葡萄球菌表面的表达导致宿主细胞与化脓性金黄色葡萄球菌相同的形态学改变。用纯化的重组单胞SfbI蛋白孵养HUVEC细胞也会引发腔样结构的积累和膜内陷的形成。SfbI蛋白被标记在胶体金颗粒上，在膜接触后显示出聚集。因此，我们的研究结果表明，宿主细胞小窝启动了A群链球菌的侵袭过程，链球菌入侵蛋白SfbI是激活小窝介导的内吞途径的触发因子。
This study identified caveolae as an entry port for group A streptococci into epithelial and endothelial cells. Scanning electron microscopy as well as ultrathin sections of infected cells demonstrated accumulation of small omega-shaped cavities in the host cell membrane close to adherent streptococci. During invasion, invaginations were formed that subsequentely revealed intracellular compartments surrounding streptococci. Caveolin-1 was shown to be present in the membrane of invaginations and the compartment membranes. These compartments were devoid of any classic endosomal/lysosomal marker proteins and can thus be described as caveosomes. Disruption of caveolae with methyl-beta-cyclodextrin and filipin abolished host cell invasion. Importantly, streptococci inside caveosomes avoid fusion with lysosomes. Expressing of SfbI protein on the surface of the non-invasive S. gordonii resulted in identical morphological alterations on the host cell as for S. pyogenes . Incubation of HUVEC cells with purified recombinant sole SfbI protein also triggered accumulation of cavity-like structures and formation of membrane invaginations. Tagged to colloidal gold-particles, SfbI protein was shown to cluster following membrane contact. Thus, our results demonstrate that host cell caveolae initiate the invasion process of group A streptococci and that the streptococcal invasin SfbI is the triggering factor that activates the caveolae-mediated endocytic pathway.