Interactome of the Type IV Secretion System of Helicobacter pylori

Abstract

Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach and is present in approximately half of the global population. Chronic infection with this microorganism is associated with a range of gastrointestinal diseases, from chronic gastritis to gastric cancer. The most virulent strains harbor a pathogenicity island of about 40 kb, composed of 28 to 30 genes that encode the type IV secretion system (T4SS), which is responsible for translocating the oncoprotein CagA into host gastric epithelial cells. The objective of this study was to analyze the interactions among the subunits that constitute the T4SS of H. pylori, to understand the functional role of each component in system assembly and in the translocation of CagA. To this end, a comprehensive review of the current state of the art on the T4SS and the functions described for each subunit was conducted. Subsequently, a protein–protein interaction analysis was performed using the STRING platform, aiming to identify functional associations and interaction networks among the system components. Based on the integration of the collected information, a partial model of the T4SS interactome was proposed. The results reveal a high degree of structural and functional complexity, with proteins classified as structural (14 subunits), energy-related components (three), chaperones (four), proteins with enzymatic activity (two), and the oncoprotein CagA. These findings contribute to a better understanding of the T4SS as a major virulence factor and to the identification of potential therapeutic targets