Merz A J, Enns C A, So M
Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, 97201-3098, USA.
Mol Microbiol. 1999 Jun;32(6):1316-32. doi: 10.1046/j.1365-2958.1999.01459.x.
The pathogenic Neisseriae Neisseria meningitidis and Neisseria gonorrhoeae, initiate colonization by attaching to host cells using type IV pili. Subsequent adhesive interactions are mediated through the binding of other bacterial adhesins, in particular the Opa family of outer membrane proteins. Here, we have shown that pilus-mediated adhesion to host cells by either meningococci or gonococci triggers the rapid, localized formation of dramatic cortical plaques in host epithelial cells. Cortical plaques are enriched in both components of the cortical cytoskeleton and a subset of integral membrane proteins. These include: CD44v3, a heparan sulphate proteoglycan that may serve as an Opa receptor; EGFR, a receptor tyrosine kinase; CD44 and ICAM-1, adhesion molecules known to mediate inflammatory responses; f-actin; and ezrin, a component that tethers membrane components to the actin cytoskeleton. Genetic analyses reveal that cortical plaque formation is highly adhesin specific. Both pilE and pilC null mutants fail to induce cortical plaques, indicating that neisserial type IV pili are required for cortical plaque induction. Mutations in pilT, a gene required for pilus-mediated twitching motility, confer a partial defect in cortical plaque formation. In contrast to type IV pili, many other neisserial surface structures are not involved in cortical plaque induction, including Opa, Opc, glycolipid GgO4-binding adhesins, polysialic acid capsule or a particular lipooligosaccharide variant. Furthermore, it is shown that type IV pili allow gonococci to overcome the inhibitory effect of heparin, a soluble receptor analogue, on gonococcal invasion of Chang and A431 epithelial cells. These and other observations strongly suggest that type IV pili play an active role in initiating neisserial infection of the mucosal surface in vivo. The functions of type IV pili and other neisserial adhesins are discussed in the specific context of the mucosal microenvironment, and a multistep model for neisserial colonization of mucosal epithelia is proposed.
致病性奈瑟菌属的脑膜炎奈瑟菌和淋病奈瑟菌，通过使用IV型菌毛附着于宿主细胞来启动定植。随后的黏附相互作用是由其他细菌黏附素介导的，特别是外膜蛋白的Opa家族。在此，我们已经表明，脑膜炎奈瑟菌或淋病奈瑟菌通过菌毛介导对宿主细胞的黏附会触发宿主上皮细胞中快速、局部形成显著的皮质斑块。皮质斑块富含皮质细胞骨架的成分以及一部分整合膜蛋白。这些包括：CD44v3，一种可能作为Opa受体的硫酸乙酰肝素蛋白聚糖；表皮生长因子受体（EGFR），一种受体酪氨酸激酶；CD44和细胞间黏附分子-1（ICAM-1），已知介导炎症反应的黏附分子；丝状肌动蛋白（f-actin）；以及埃兹蛋白（ezrin），一种将膜成分与肌动蛋白细胞骨架相连的成分。遗传学分析表明，皮质斑块的形成具有高度的黏附素特异性。pilE和pilC基因缺失突变体均不能诱导皮质斑块形成，这表明奈瑟菌IV型菌毛是诱导皮质斑块所必需的。pilT基因发生突变，该基因是菌毛介导的颤动运动所必需的，会导致皮质斑块形成出现部分缺陷。与IV型菌毛不同，许多其他奈瑟菌表面结构不参与皮质斑块的诱导，包括Opa、Opc、糖脂GgO4结合黏附素、多聚唾液酸荚膜或一种特定的脂寡糖变体。此外，研究表明IV型菌毛使淋病奈瑟菌能够克服可溶性受体类似物肝素对其侵袭Chang和A431上皮细胞的抑制作用。这些以及其他观察结果强烈表明，IV型菌毛在体内启动奈瑟菌对黏膜表面的感染中发挥积极作用。我们在黏膜微环境的特定背景下讨论了IV型菌毛和其他奈瑟菌黏附素的功能，并提出了一个奈瑟菌在黏膜上皮定植的多步骤模型。
