Abstract

GUTIERREZ E, Andrés Julián  and  BAYONA R, Martín Alonso. Topological analysis of the interactome of Helicobacter pylori reveals topologically essential proteins: identification of therapeutic targets. Rev Col Gastroenterol [online]. 2014, vol.29, n.1, pp.36-45. ISSN 0120-9957.

Helicobacter pylori, which have colonized half the world’s population, have a prevalence of 70% to 90 % in developing countries and 25% to 50 % in industrialized countries. It is well established that the infection is associated with the development of chronic gastritis, gastric and duodenal ulcers and stomach cancer in humans. Helicobacter pylori were the first pathogenic bacteria whose interactome was deduced. Topologic analysis identified 702 proteins involved in 1,359 interactions coverage of 97.7 % with scale-free networks. In other words, the interactome contains topologically essential proteins, however, because these proteins and their physiological associations have not been described, we cannot identify potential therapeutic targets. To identify topologically essential proteins we reconstructed the interactome of H. pylori strain ATCC 26695 using BioNetBuilder and Cytoscape NetworkAnalyzer the cytoHubba web application. The reconstruction presented 896 proteins and 2416 interactions with a coverage of 96 % of the proteome adjusted to the distribution of the power law. In other words, the reconstruction presented a scale-free network. We used NetworkAnalyzer and the Hubba application to identify essential proteins according to the BC and K parameters. On that basis we constructed a subnetwork. Analysis of this subnetwork showed that the type IV secretion system interacts with metabolic subsystems of lipids, amino acids and nucleic acids by means of proteins for which this interaction has not been suggested. Moreover, these interactions can be explained by profiles of expression that are dependent on pH, adhesion and iron homeostasis. This allows us to complements both the basic biology of the strain as well as to postulate putative new therapeutic targets.

Keywords : Helicobacter pylori; interactome; graph theory; topological nodes; type IV secretion system; therapeutic target.

        · abstract in Spanish     · text in English | Spanish     · English ( pdf ) | Spanish ( pdf )