志贺毒素噬菌体遗传多样性及其导致新菌型的机制研究

产志贺毒素大肠埃希菌（Shiga toxin-producing Escherichia coli，STEC）是一类能引起人感染性腹泻、出血性肠炎及溶血性尿毒综合征的重要食源性病原菌。志贺毒素是STEC最主要的致病物质，由志贺毒素前噬菌体编码。目前有超过200余种血清型大肠埃希菌可携带志贺毒素，引起人类疾病，其中O157:H7是流行最广致病力最强的血清型，但近年来由新血清型STEC引起的散发感染和暴发不断增多。目前尚不清楚由志贺毒素噬菌体导致新致病菌型出现的机制。本项目拟分析我国不同来源志贺毒素噬菌体基因组结构、染色体插入位点；筛查影响志贺毒素噬菌体可诱导性及志贺毒素表达水平的关键基因或调控区域；了解不同志贺毒素噬菌体对大肠埃希菌转染能力及影响转染的细菌表面结构；探讨志贺毒素噬菌体导致新菌型的可能机制。

Shiga toxin-producing Escherichia coli (STEC) are an emerging group of foodborne pathogens that can cause human illness ranging from non-bloody diarrhea to hemorrhagic colitis (HC) and sometimes fatal hemolytic uremic syndrome (HUS) complications. Shiga toxin (Stx) is the most critical virulence factor of STEC, encoded by Stx-converting bacteriophages. More than 200 serotypes E.coli that harbor Stx phage have been associated with human illness, among which O157:H7 was the most popular and virulent serotype. Currently, there is growing concern over the emergence of new serotype infections and outbreaks. However, it is still unclear how the new pathotype arise by the Stx-converting bacteriophages. In this project, we will analysis the genomic structure and insertion site of Stx phage; investigate the key genes and regulatory region associated with the inducibility and the expression level of shiga toxin; study the transfection level of different Stx phage on E.coli and bacterial surface structure that affect transfection; and explore the mechanisms how the new pathotype arise by Stx-converting bacteriophages.