PTS-mediated virulence regulation in Neisseria meningitidis

PTS介导的脑膜炎奈瑟菌毒力调节

• 批准号: 29898343
• 负责人: Professor Dr. Jörg Stülke
• 金额: --
• 依托单位: INRA
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/29898343?language=en
• 关键词: PTS; mediated; virulence; regulation; Neisseria

Neisseria meningitidis, the causative agent of meningitis, is a pathogen constantly present in the nasopharynx of a large part of any human population (in Europe between 5 and 20%). For reasons barely understood, it occasionally enters the blood stream and can even cross the brain-blood barrier, thereby causing severe infections. Despite antibiotic treatment, 10% of the severe infections have a fatal outcome. Mutations affecting certain PTS components (hprK and ptsff) have been shown to diminish the virulence of N. meningitidis. In response to the carbon metabolic state of bacteria, PTS proteins in the cells are more or less phosphorylated. Because N. meningitidis encounters quite different concentrations of glucose in the various tissues it can colonise, the PTS-mediated signal is thought to be important for the adhesion to epithelial and endothelial cells. The effect of the PTS proteins is likely to be mediated via YhbJ and the sigma factor RpoN. Protein/protein interaction studies will confirm or refute this hypothesis. Transcriptome and proteome analyses of mutants affected in PTS proteins and exhibiting a diminished virulence are expected to allow the identification of the complete signal transduction pathway underlying the carbon metabolism-dependent control of N. meningitidis virulence. A detailed understanding of this signal transduction pathway is expected to allow in the long term the development of new antimicrobial agents affecting PTS proteins, which occur exclusively in bacteria.

脑膜炎奈瑟氏菌是脑膜炎的病原体，是一种经常存在于大部分人群鼻咽部的病原体（在欧洲为5%至20%）。由于几乎不了解的原因，它偶尔会进入血液，甚至可以穿过脑血屏障，从而导致严重的感染。尽管进行了抗生素治疗，但10%的严重感染仍有致命的结局。影响某些PTS组分（hprK和ptsff）的突变已被证明会降低N.脑膜炎响应于细菌的碳代谢状态，细胞中的PTS蛋白质或多或少地被磷酸化。因为N.尽管脑膜炎在其能够定植的各种组织中遇到相当不同浓度的葡萄糖，但PTS介导的信号被认为对于粘附到上皮细胞和内皮细胞是重要的。PTS蛋白的作用可能通过YhbJ和σ因子RpoN介导。蛋白质/蛋白质相互作用研究将证实或反驳这一假设。对PTS蛋白中受影响的突变体进行转录组和蛋白质组分析，并显示出减弱的毒力，预计可以鉴定N.脑膜炎毒力对这种信号转导途径的详细了解有望长期开发影响PTS蛋白的新抗菌剂，PTS蛋白仅发生在细菌中。

项目成果

Essential Role of the hprK Gene in Ralstonia eutropha H16

• DOI: 10.1159/000233505
• 发表时间: 2009-08
• 期刊: Journal of Molecular Microbiology and Biotechnology
• 影响因子: 1.2
• 作者: Désirée Krauβe;K. Hunold;B. Kusian;O. Lenz;J. Stülke;B. Bowien;J. Deutscher