Identification of Interaction Partners of Outer Inflammatory Protein A: Computational and Experimental Insights into How Helicobacter pylori Infects Host Cells

Adherence to the gastric epithelium is an essential feature of Helicobacter pylori for its colonization. Outer membrane proteins (OMPs) play a pivotal role in adherence potentiating the survival of the microbe in the gastric tissue. Among these proteins, Outer inflammatory protein A (OipA) is a critical protein that is known to help bacteria to colonize on the host gastric epithelial cell surface. Although the role of OipA in the H. pylori attachment and the association between OipA-positive H. pylori strains and clinical outcomes have been demonstrated, there is limited information on the structural mechanism of the OipA action in the adherence of H. pylori to the gastric epithelial cell surface. Our study utilizes experimental and computational methodologies to investigate the interaction partners of OipA on the gastric epithelial cell surface. Initially, we performed a proteomic analysis to decipher the OipA interactome in the human gastric epithelial cells using a pull-down assay of the recombinant OipA and the membrane proteins of the gastric epithelial cells. Proteomic analysis has revealed 704 unique proteins that interacted with OipA. We have further analyzed 16 partners of OipA using molecular modeling tools. Structural findings obtained from the prediction of the protein-protein complexes of OipA and candidate partners unraveled 3 human proteins whose OipA interactions could base an explanation about how H. pylori recruits OipA for adherence. Altogether, the findings presented here provide insights into novel mechanisms of H. pylori and host interactions through OipA, reflecting the potential of these mechanisms and interactions as therapeutic targets to combat H. pylori infection. Key pointsO_LIOuter membrane proteins (OMPs) are an emerging topic in bacterial infection. C_LIO_LIOipA is a candidate for an adherence-receptor network on the gastric epithelial cell surface with H. pylori. C_LIO_LIOipA interactome partners on gastric epithelial cell surfaces are valuable therapeutic targets for the H. pylori infection. C_LI