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Neisseria meningitidis Polynucleotide Phosphorylase Affects Aggregation, Adhesion, and Virulence

机译:脑膜炎奈瑟氏球菌多核苷酸磷酸化酶影响聚集,粘附和毒力。

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Neisseria meningitidis autoaggregation is an important step during attachment to human cells. Aggregation is mediated by type IV pili and can be modulated by accessory pilus proteins, such as PilX, and posttranslational modifications of the major pilus subunit PilE. The mechanisms underlying the regulation of aggregation remain poorly characterized. Polynucleotide phosphorylase (PNPase) is a 3′–5′ exonuclease that is involved in RNA turnover and the regulation of small RNAs. In this study, we biochemically confirm that NMC0710 is the N. meningitidis PNPase, and we characterize its role in N. meningitidis pathogenesis. We show that deletion of the gene encoding PNPase leads to hyperaggregation and increased adhesion to epithelial cells. The aggregation induced was found to be dependent on pili and to be mediated by excessive pilus bundling. PNPase expression was induced following bacterial attachment to human cells. Deletion of PNPase led to global transcriptional changes and the differential regulation of 469 genes. We also demonstrate that PNPase is required for full virulence in an in vivo model of N. meningitidis infection. The present study shows that PNPase negatively affects aggregation, adhesion, and virulence in N. meningitidis.
机译:脑膜炎奈瑟氏球菌的自动聚集是附着在人类细胞上的重要步骤。聚集由IV型菌毛介导,并且可以由辅助菌毛蛋白(例如PilX)和主要菌毛亚基PilE的翻译后修饰来调节。聚集调节的基础机制仍然不明确。多核苷酸磷酸化酶(PNPase)是一种3'-5'核酸外切酶,参与RNA转换和小RNA的调控。在这项研究中,我们通过生物化学方法确认NMC0710是脑膜炎奈瑟氏菌PNPase,并表征其在脑膜炎奈瑟氏菌发病机理中的作用。我们表明,编码PNPase的基因的删除导致过度聚集并增加对上皮细胞的粘附。发现诱导的聚集依赖于菌毛并且由过多的菌毛捆绑介导。细菌附着于人细胞后,诱导PNPase表达。 PNPase的删除导致全球转录变化和469基因的差异调节。我们还证明,在脑膜炎奈瑟氏球菌感染的体内模型中,完全毒力需要PNPase。本研究表明,PNPase对脑膜炎奈瑟氏球菌的聚集,粘附和毒力具有负面影响。

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