Functional characterisation of a novel type IV secretion system associated with the severe disease marker, dupA

幽门螺杆菌是一种常见的细菌感染的人类胃，影响约一半的世界？的人口。在大多数人中，感染是无害的，然而，在约20%的感染者中，H。幽门导致严重的疾病，包括胃/十二指肠溃疡和胃癌。在H. pylori基因组已被证明是与H.幽门感染我们已经证明，这些标记是一个单一的大簇基因的一部分，这些基因编码的蛋白质已知组装成一个专门的细菌？第四型？分泌系统（T4 SS）。细菌T4 SS的功能是在遗传物质交换中将蛋白质-DNA复合物转运到其他细菌细胞中，或者在引起植物疾病的细菌的情况下，其功能是将细菌DNA转运并整合到宿主植物细胞染色体中。后一个过程在遗传上转化植物细胞并引发疾病的发展。幽门螺杆菌T4 SS基因与疾病的关系以及T4 SS基因簇中某些成分的存在，我们称之为tfs 4，我们假设tfs 4可以类似地将蛋白质-DNA复合物转运到人类胃内的感染细胞中。我们建议确定tfs 4活性（开/关状态）是否同样与从感染个体分离的菌株中的疾病表现相关，并充分研究tfs 4的功能。在植物病原体中，一种称为VirD 2的蛋白质负责将细菌DNA运输和整合到宿主植物细胞染色体中。H. pylori tfs 4编码类似的VirD 2蛋白。我们将确定tfs 4 VirD 2结合的其他蛋白质和特定DNA序列，并确定它是否可以通过新的H. pylori T4 SS对不同类型的人胃细胞的作用。这可能揭示了一种新的、未被描述的、极其重要的潜在机制，H。幽门螺旋杆菌可引致严重疾病，例如某些受感染人士患上胃癌。我们的工作对于确定H.幽门螺杆菌具有最大的致病潜力，并可能为将来如何利用Tfs 4 T4 SS治疗胃病提供见解。我们的观察结果将发表在科学媒体上，在我们的公开网站上，并可能通过我们的新闻办公室传达给国家媒体，以吸引和激发公众的广泛关注。

Helicobacter pylori is a common bacterial infection of the human stomach, affecting approximately half of the world?s population. In most people the infection is harmless, however, in ~20% of infected individuals, H. pylori causes serious disease, including gastric/duodenal ulcers, and gastric cancer. The presence of several genes encoded within the H. pylori genome have been shown to be putative markers for the development of severe disease coincident with H. pylori infection. We have shown that these markers are part of a single large cluster of genes which encode proteins known to assemble into a specialised bacterial ?type IV? secretion system (T4SS). Bacterial T4SSs function to transport protein-DNA complexes into other bacterial cells in the exchange of genetic material, or in the case of bacteria which cause diseases in plants, function to transport and integrate bacterial DNA into the host plant cell chromosome. This latter process genetically transforms the plant cell and initiates the development of disease.Due to previously established association of individual H. pylori T4SS genes with disease and the presence of certain components within the T4SS gene cluster, which we call tfs4, we hypothesise that tfs4 may similarly transport protein-DNA complexes into infected cells within the human stomach. We propose to determine whether tfs4 activity (on/off status) similarly associates with disease presentation in strains isolated from infected individuals and to fully investigate the function of tfs4. In plant pathogens, a protein called VirD2 is responsible for the transport and integration of bacterial DNA into the host plant cell chromosome. H. pylori tfs4 encodes a similar VirD2 protein. We will determine what other proteins and specific DNA sequences tfs4 VirD2 binds to and establish whether it can be transported, in complex with bacterial DNA, via the novel H. pylori T4SS to different types of human gastric cells. This may reveal a novel, uncharacterised and extremely important underlying mechanism by which H. pylori is able to cause serious diseases, such as gastric cancer in some infected individuals. Our work will be important for determining which strains of H. pylori have the most potential for causing disease and may provide insight into how the tfs4 T4SS can be exploited in future for the treatment of gastric disorders. Our observations will be published in the scientific press, on our publicly accessible websites and potentially also communicated to the national media via our Press Office to capture and stimulate broad public attention.