There is a strong correlation between some pathogens and certain cancer types. One example is Helicobacter pylori and gastric cancer. Exactly how they contribute to host tumorigenesis is, however, a mystery. Pathogens often interact with the host through proteins. To subvert defense, they may mimic host proteins at the sequence, structure, motif, or interface levels. Interface similarity permits pathogen proteins to compete with those of the host for a target protein and thereby alter the host signaling. Detection of host–pathogen interactions (HPIs) and mapping the re-wired superorganism HPI network—with structural details—can provide unprecedented clues to the underlying mechanisms and help therapeutics. Here, we describe the first computational approach exploiting solely interface mimicry to model potential HPIs. Interface mimicry can identify more HPIs than sequence or complete structural similarity since it appears more common than the other mimicry types. We illustrate the usefulness of this concept by modeling HPIs of H. pylori to understand how they modulate host immunity, persist lifelong, and contribute to tumorigenesis. H. pylori proteins interfere with multiple host pathways as they target several host hub proteins. Our results help illuminate the structural basis of resistance to apoptosis, immune evasion, and loss of cell junctions seen in H. pylori-infected host cells.
- computational prediction of host–pathogen interactions
- interface mimicry
- protein–protein interaction
- structural network
- superorganism network