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HP1230-potential regulatory protein of H. pylori chromosome replication


Helicobacter pylori is a microaerophilic, Gram negative pathogenic bacterium. It colonizes human stomach and has been recognized as a causative agent of gastric and duodenal inflammation, peptic ulcer and gastric cancer. It was discovered 20 years ago and since then extensive studies have been carried out leading mainly to its pathogenesis mechanisms explanation.

In spite of the fact, that the genome sequence of the two H. pylori strains was established, most of the basic metabolic pathways are still not fully recognized. One of them is initiation and regulation of H. pylori chromosome replication. The key elements of the H. pylori chromosome initiation replication were identified: DnaA protein and oriC region, and their interactions were characterized in vitro.

However, it is still not known which elements are involved in regulation of initiation of its chromosome replication. Presumably, the DnaA activity is regulated by ATP/ADP binding, like in other bacteria. Probably, the cytoplasmic concentration of the DnaA protein is controlled by DnaA-membranes interaction, but it is still not known, how the DnaA protein is bound to the membranes.

We assume that H. pylori DnaA protein is localized in the inner membranes of the cell via HP1230 protein interaction. A gene homologous to HP1230 was also identified on the chromosomes of Helicobacter hepaticus, Campylobacter jejuni and Wolinella succinogenes, bacteria closely related to H. pylori.

The main objective of the project is to study the role of the HP1230 protein as a potential regulatory protein of H. pylori chromosome replication. It may also be a common regulatory strategy present in all bacteria belonging to the epsilon subclass of proteobacteria.

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