Mechanism of Helicobacter pylori DNA exchange and microcin delivery

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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.