Variable disruption of epithelial monolayers by Neisseria meningitidis carriage isolates of the hypervirulent MenW cc11 and MenY cc23 lineages.

Variable disruption of epithelial monolayers by Neisseria meningitidis carriage isolates of the hypervirulent MenW cc11 and MenY cc23 lineages.
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DOI:
10.1099/mic.0.001305
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发表时间:
2023-02
期刊:
影响因子:
2.8
通讯作者:
Bayliss, Christopher D.
Bayliss, Christopher D.
中科院分区:
生物学4区
文献类型:
--
作者:
Dave, Neelam;Albiheyri, Raed S.;Wanford, Joseph J.;Green, Luke R.;Oldfield, Neil J.;Turner, David P. J.;Martinez-Pomares, Luisa;Bayliss, Christopher D.

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粘膜组织定植 脑膜炎奈瑟菌 需要IV型菌毛和多种外膜蛋白介导的粘附。粘膜的穿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,我们检测了两种克隆复合物的携带分离物的粘附、侵袭和单层破坏, N.脑膜炎血清群Y cc 23和高毒力血清群W cc 11谱系的携带分离株均表现出高水平的细胞粘附,并且在独立分离株中具有可变的破坏表型。在多个cc 11分离株中,编码主要菌毛亚单位的基因失活可消除粘附能力和破坏上皮单层的能力。相反,失活的相位可变opa或nadA基因减少粘附和侵袭,但不破坏单层完整性。组织破坏性脑膜炎球菌的粘附与紧密连接蛋白occludin的染色丧失相关。有趣的是,在菌毛阴性的菌株背景下,我们观察到opa基因的补偿性开启开关,这有助于持续粘附。我们的结论是,破坏上皮单层发生在多种脑膜炎球菌谱系,但可以在运输过程中有所不同,并与菌毛介导的粘附密切相关。
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.
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