Molecular basis of O-antigen modification and genomics of serotype-converting bacteriophages of Shigella flexneri

全世界每年约有1.65亿个志贺氏菌病病例，导致110万人死亡。大多数病例发生在发展中国家，大多数死亡病例发生在5岁以下儿童。志贺氏菌病主要由福氏志贺氏菌引起。福氏志贺菌有13种不同的血清型，由称为O抗原的细菌细胞表面多糖确定。细菌病毒(噬菌体)携带赋予O-抗原变异的基因。感染和病毒随后并入细菌细胞的遗传物质会导致细菌O抗原的修饰。这种噬菌体介导的O抗原修饰导致了不同的血清型。该项目将解决与O-抗原修饰相关的基本过程。这将通过研究O-抗原修饰基因簇编码的酶的结构和功能来实现。我们已经从福氏志贺氏菌中分离出了几个转换血清型的噬菌体，我们计划对它们的基因组信息进行比较和表征，以增加对它们的起源和与细菌宿主的关系的了解。

There are approximately 165 million cases of shigellosis world wide annually, resulting in 1.1 million deaths. The majority of cases occur in developing countries and most deaths occur in children under 5 years of age. Shigellosis is mainly caused by the bacterium Shigella flexneri. There are 13 different serotypes of S. flexneri determined by bacterial cell-surface polysaccharides called O-antigens. Bacterial viruses (bacteriophages) carry the genes which confer O-antigen variation. Infection and subsequent incorporation of the virus into the genetic material of the bacterial cell result in modification of the bacterial O-antigen. This phage-mediated O-antigen modification gives rise to different serotypes. The project will address fundamental processes related to the O-antigen modification. This will be achieved by studying structure and function of the enzymes encoded by the O-antigen modification gene cluster. We have isolated several serotype-converting bacteriophages from S. flexneri and we plan to compare and characterise their genomic information to increase understanding of their origin and relationship with the bacterial host.