PTS-mediated virulence regulation in Neisseria meningitidis

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的鼻咽中的病原体(在欧洲占5%至20%)。由于鲜为人知的原因，它偶尔会进入血液流动，甚至可以越过脑-血屏障，从而导致严重感染。尽管接受了抗生素治疗，但10%的严重感染会导致致命后果。影响某些PTS成分(hprK和ptsff)的突变已被证明会降低脑膜炎奈瑟菌的毒力。为了响应细菌的碳代谢状态，细胞中的PTS蛋白或多或少被磷酸化了。由于脑膜炎奈瑟氏菌在其定植的不同组织中遇到不同浓度的葡萄糖，PTS介导的信号被认为对与上皮细胞和内皮细胞的黏附具有重要作用。PTS蛋白的作用可能是通过YhbJ和Sigma因子RpoN介导的。蛋白质/蛋白质相互作用研究将证实或驳斥这一假设。对受PTS蛋白影响并表现出毒力减弱的突变体的转录组和蛋白质组分析有望识别脑膜炎奈瑟氏菌毒力依赖碳代谢控制的完整信号转导途径。从长远来看，对这一信号转导途径的详细了解将使开发影响PTS蛋白的新的抗菌剂成为可能，这种蛋白只在细菌中存在。

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.