Glycosylation of pili in pathogenic Neisseria: function in disease and potential as a vaccine antigen

由B群脑膜炎奈瑟菌和淋病奈瑟菌引起的疾病仍然是世界范围内的一个重大卫生问题。目前还没有针对这两种细菌的疫苗。在这些细菌上发现的一种被称为菌毛的表面结构是宿主定植和疾病的关键。遗传学和结构研究已经确定，构成菌毛的蛋白质亚基是糖基化的——通过添加糖进行修饰。糖基化在疾病过程中的作用尚不清楚。毛的糖基化可能是附着于宿主细胞或逃避免疫系统所必需的。在我们目前的研究中，我们已经确定并分析了一些参与菌毛糖基化的基因，这些基因在细菌中产生已知的结构。我们还发现了一系列新的基因，我们相信这些基因也与糖基化有关。其中一些基因参与未知结构的生物合成，在从脑膜炎患者分离的细菌中很常见。我们将鉴定这些结构并表征这些基因失活的细菌，以便我们可以检查菌毛糖基化在定植和疾病中的作用。这项研究有可能产生关于定植和疾病过程的重要新信息，也有可能促进疫苗开发的新方法。

Disease caused by Group B Neisseria meningitidis and Neisseria gonorrhoeae remain a significant health problem worldwide. There are currently no vaccines available for either of these bacteria. A surface structure found on these bacteria, called pili, are key in host colonisation and disease. Genetics and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. The role of glycosylation in the disease process is not known. It is possible that the glycosylation of pili is required for attachment to host cells or perhaps in evasion of the immune system. In our current studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria which make structre that are know. We have also identified a series of new genes we believe are also involved in glycosylation. Some of these genes are involved in the biosynthesis of unknown structures and are common in bacteria isolated from patients with meningitis. We will identify these stuctures and characterise bacteria in which these genes have been inactivated so that we can examine the role of pili glycosylation in colonisation and disease. This study has the potential to yield important new information about the process of colonisation and disease, and also has the potential to facilitate novel approaches in vaccine development.