Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells
Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells
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DOI：
10.1111/j.1365-2958.2007.05630.x
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发表时间：
2007-04-01
影响因子：
3.6
通讯作者：
Hung Ton-That
中科院分区：
文献类型：
--
作者：
Mandlik, Anjali;Swierczynski, Arlene;Hung Ton-That
药丸介导的对宿主组织的粘附对于许多细菌病原体感染的建立至关重要。白喉棒杆菌在其表面组装了三个不同的菌毛结构。然而，人们对各种菌毛如何介导依从性的功能和机制仍然知之甚少。在这里，我们证明 SpaA 型菌毛足以使棒状杆菌特异性粘附到人咽上皮细胞。编码形成菌毛轴的主要菌毛蛋白的 spaA 基因的缺失会消除菌毛组装，但不会破坏咽细胞的粘附。相比之下，当轻微的pilin SpaB 或SpaC 缺失时，依从性会大大降低。针对 SpaB 或 SpaC 的抗体可阻止细菌粘附。与次要菌毛蛋白的直接作用一致，涂有 SpaB 或 SpaC 蛋白的乳胶珠与咽细胞特异性结合。因此，棒状杆菌对咽细胞的组织向性是由特定的小菌毛蛋白控制的。重要的是，免疫电子显微镜和免疫荧光研究揭示了锚定在细胞表面的小菌毛蛋白簇。在没有菌毛轴的情况下。因此，小菌毛蛋白除了并入菌毛结构之外，还可以锚定在细胞壁上，这有助于在细菌感染期间与宿主细胞紧密结合。
Adherence to host tissues mediated by pill is pivotal in the establishment of infection by many bacterial pathogens. Corynebacterium diphtheriae assembles on its surface three distinct pilus structures. The function and the mechanism of how various pili mediate adherence, however, have remained poorly understood. Here we show that the SpaA-type pilus is sufficient for the specific adherence of corynebacteria to human pharyngeal epithelial cells. The deletion of the spaA gene, which encodes the major pilin forming the pilus shaft, abolishes pilus assembly but not adherence to pharyngeal cells. In contrast, adherence is greatly diminished when either minor pilin SpaB or SpaC is absent. Antibodies directed against either SpaB or SpaC block bacterial adherence. Consistent with a direct role of the minor pilins, latex beads coated with SpaB or SpaC protein bind specifically to pharyngeal cells. Therefore, tissue tropism of corynebacteria for pharyngeal cells is governed by specific minor pilins. Importantly, immunoelectron microscopy and immunofluorescence studies reveal clusters of minor pilins that are anchored to cell surface. in the absence of a pilus shaft. Thus, the minor pilins may also be cell wall anchored in addition to their incorporation into pilus structures that could facilitate tight binding to host cells during bacterial infection.