Mechanism of Helicobacter pylori DNA exchange and microcin delivery

幽门螺杆菌感染与许多胃十二指肠疾病有关，包括慢性胃炎、消化性溃疡、腺癌和粘膜相关淋巴组织淋巴瘤。约50%的临床H.幽门螺杆菌分离物携带大小和基因含量高度可变的质粒，然而，这些质粒的生物学功能在很大程度上是未知的。隐型H的一个亚群。pylori质粒携带DNA动员（mob）基因、一种推定的新型毒素-抗毒素（TA）系统以及编码推定的细菌微菌素的操纵子。本课题主要研究以下几个方面：（1）H. pylori质粒pHel 4的结构和功能;幽门。我们希望鉴定一种新的质粒转移系统，因为迄今为止已知的IV型分泌系统（T4 SS）在H。pylori供体菌株，如cag-PAI和comB系统，不参与质粒转移。我们将研究一个编码七个氨基酸的基因，它可以合成一种修饰的七肽小肽，并研究其遗传调控。本文将分析微球蛋白自身耐受和分泌的机制、微球蛋白的靶生物以及微球蛋白在靶细胞中的作用方式。将使用适当的动物模型在体内评估DNA转移和小菌素产生。

Helicobacter pylori infection is associated with a number of gastroduodenal diseases, including chronic gastritis, peptic ulcers, adenocarcinoma and mucosa-associated-lymphoid tissue lymphoma. About 50% of clinical H. pylori isolates carry plasmids of highly variable size and gene content, however, the biological function of these plasmids is largely unknown. A subgroup of cryptic H. pylori plasmids carry DNA mobilization (mob) genes, a putative novel toxin-antitoxin (TA) system as well as an operon encoding a putative bacterial microcin. In this project we are interested to understand (1) the DNA transfer and plasmid maintenance functions in H. pylori plasmid pHel4 and (2) the structure and function of a putative plasmid-encoded microcin of H. pylori. We expect to identify a novel plasmid transfer system, since so far known type IV secretion systems (T4SS) in the H. pylori donor strain, such as the cag-PAI and the comB system, are not involved in plasmid transfer. A putative seven amino acid-encoding gene for the synthesis of a modified heptapeptide microcin and its genetic regulation will be studied. The mechanism of microcin self-tolerance and secretion, the microcin target organisms and its mode of action in target cells will be analyzed. Both, DNA transfer and microcin production will be assessed in vivo using appropriate animal models.