Molekular mechanism of horizontal gene transfer in pathogenic epsilon-proteobacteria

从环境中摄取DNA是获得新的遗传物质的第一步，包括抗生素耐药性和毒力特征，使细菌能够适应不断变化的宿主环境。本项目将在体内和体外研究ε-变形菌DNA摄取的分子机制。以两种重要的人类病原体——胃癌病原体幽门螺杆菌和人类腹泻的主要原因空肠弯曲杆菌为例，将在单细胞水平上可视化DNA在细胞膜内外运输的分子过程。先前确定参与这些病原体自然转化的基因产物将根据其在这一多步骤过程中的具体作用进行功能表征。由于这两种病原体是进化上的近亲，但实施完全不同的DNA摄取系统，它们可以作为模式生物来解读革兰氏阴性细菌DNA摄取的差异和共同原理。这一知识将使我们更深入地了解DNA摄取的分子机制，并可能导致合理开发用于自然转化的抑制剂，减少细菌宿主的适应和耐药性的传播。

DNA uptake from the environment is the first step for acquisition of new genetic material, including antibiotic resistances as well as virulence traits, enabling bacteria to adapt to changing host environments. In this project, the molecular mechanism of DNA uptake in ε-proteobacteria will be addressed in vitro and in vivo. Taking two important human pathogens, the gastric cancer agent, Helicobacter pylori, and the major cause for human diarrhoea, Campylobacter jejuni, the molecular process of DNA transport across outer and inner membrane will be visualized on the single cell level. Gene products previously identified to be involved in natural transformation in these pathogens will be functionally characterized in respect to their specific role in this multi-step process. Since both pathogens are evolutionary close relatives, but implement completely different DNA uptake systems, they serve as model organisms to decipher differences and common principles of Gram-negative bacterial DNA uptake. This knowledge will give more insight into the molecular mechanism of DNA uptake and may lead to the rational development of inhibitors for natural transformation, reducing bacterial host adaptation and spread of resistances.