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Abstract：
Colonization of mucosal tissues by Neisseria meningitidis requires adhesion mediated by the type IV pilus and multiple outer-membrane proteins. Penetration of the mucosa and invasion of epithelial cells are thought to contribute to host persistence and invasive disease. Using Calu-3 cell monolayers grown at an air-liquid interface, we examined adhesion, invasion and monolayer disruption by carriage isolates of two clonal complexes of N. meningitidis. Carriage isolates of both the serogroup Y cc23 and the hypervirulent serogroup W cc11 lineages exhibited high levels of cellular adhesion, and a variable disruption phenotype across independent isolates. Inactivation of the gene encoding the main pilus sub-unit in multiple cc11 isolates abrogated both adhesive capacity and ability to disrupt epithelial monolayers. Contrastingly, inactivation of the phase-variable opa or nadA genes reduced adhesion and invasion, but not disruption of monolayer integrity. Adherence of tissue-disruptive meningococci correlated with loss of staining for the tight junction protein, occludin. Intriguingly, in a pilus-negative strain background, we observed compensatory ON switching of opa genes, which facilitated continued adhesion. We conclude that disruption of epithelial monolayers occurs in multiple meningococcal lineages but can vary during carriage and is intimately linked to pilus-mediated adhesion.
摘要：
脑膜炎奈瑟氏菌对粘膜组织的定植需要由IV型菌毛和多种外膜蛋白介导的粘附。粘膜的渗透和上皮细胞的侵入被认为有助于宿主的持久性和侵袭性疾病。使用在气液界面生长的Calu-3细胞单层，我们检查了附着力，两种脑膜炎奈瑟氏球菌克隆复合物的携带分离株的侵袭和单层破坏。血清群Ycc23和高毒力血清群Wccc11谱系的运输分离株均表现出高水平的细胞粘附，和独立分离株之间的可变破坏表型。多个cc11分离株中编码主要菌毛亚基的基因的失活消除了粘附能力和破坏上皮单层的能力。相反，相位可变的opa或nadA基因的失活减少了粘附和侵袭，但不破坏单层的完整性。组织破坏性脑膜炎球菌的粘附与紧密连接蛋白的染色丢失相关，occludin.有趣的是，在菌毛阴性菌株背景下，我们观察到opa基因的补偿性ON转换，这促进了持续的粘附。我们得出的结论是，上皮单层的破坏发生在多个脑膜炎球菌谱系中，但在运输过程中可能会有所不同，并且与菌毛介导的粘附密切相关。
