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全世界的一个重大健康问题。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表面结构，称为菌毛，是宿主定植和疾病的关键。遗传学和结构研究已经证实，组成菌毛的蛋白质亚单位是糖基化的--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。菌毛的糖基化可能是连接宿主细胞所必需的，也可能是逃避免疫系统所必需的。在我们目前的研究中，我们已经在细菌中鉴定和分析了一些与菌毛糖基化有关的基因，这些基因构成了已知的结构。我们还发现了一系列我们认为也与糖基化有关的新基因。其中一些基因参与未知结构的生物合成，在脑膜炎患者分离的细菌中很常见。我们将识别这些结构并描述这些基因已经失活的细菌，这样我们就可以研究菌毛糖基化在定植和疾病中的作用。这项研究有可能获得关于殖民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.