MOLECULAR ANALYSIS OF VIRULENCE FACTORS OF GROUP B STREPTOCOCCI

无乳链球菌，通常被称为B组链球菌(GBS)，是新生儿最常见的危及生命的感染(特别是菌血症、肺炎和脑膜炎)。即使在可以随时获得抗菌治疗的发达国家，死亡率也很高。尽管GBS病很重要，但生物体侵袭和破坏宿主组织的确切分子机制却知之甚少。该项目的长期目标是全面了解GBS疾病的发病机制，并将其应用于改进的预防策略的开发。我们建议对编码GBS毒力决定因素的基因进行全面的分子表征，特别是那些编码黏附和入侵宿主细胞能力的基因。将构建携带这些基因特定突变的GBS，并将它们的毒力与其他相同基因的亲本GBS的毒力进行比较。这将使我们能够确定每个假定的毒力因子在疾病发病机制中的确切贡献。此外，将对在这一过程中重要的蛋白质进行疫苗潜力测试。

Streptococcus agalactiae, more commonly referred to as group B streptococcus (GBS), is the commonest cause of life-threatening infection (specifically bacteraemia, pneumonia and meningitis) in neonates. Mortality is high even in developed countries where antimicrobial therapy is readily available. In spite of the importance of GBS disease, the precise molecular mechanisms whereby the organism colonizes, invades and damages host tissues are poorly understood. The long term goal of this project is to gain a complete understanding of the pathogenesis of GBS disease and to apply this to development of improved preventative strategies. We propose to carry out a comprehensive molecular characterization of genes encoding putative GBS virulence determinants, with particular reference to those which encode the capacity to adhere to and invade host cells. GBS carrying defined mutations in these genes will be constructed and their virulence will be compared with that of the otherwise isogenic parental GBS. This will enable us to determine the precise contribution of each putative virulence factor to the pathogenesis of disease. Moreover, proteins shown to be important in this process will be tested for vaccine potential.