Investigating Host-Bacterial Interactions Among Enteric Pathogens

Background: Enteric bacterial pathogens remain a major cause of morbidity and mortality worldwide, particularly in developing countries. Disease pathogenesis is critically influenced by host–pathogen proteinprotein interactions (HPIs), which enable bacterial survival, immune evasion, and intracellular persistence. Comparative analysis of HPIs across multiple enteric pathogens provides valuable insights into conserved and pathogen-specific virulence strategies. Aim: To investigate and compare host–pathogen protein–protein interaction (HPI) profiles among major enteric bacterial genera—Escherichia, Shigella, Salmonella, and Vibrio—using a previously validated in silico prediction framework. Methods: An in silico HPI prediction pipeline was employed to evaluate interactions between human host proteins and representative strains of Escherichia coli, Shigella spp., Salmonella spp., and Vibrio spp. Comparative analyses were performed to identify common HPIs, genus-specific interactions, and inter-species variations. Functional enrichment analysis of host targets was conducted to elucidate biological pathways affected by pathogen interactions. Results: Despite genus- and species-specific variations, a conserved repertoire of HPIs targeting host immune signaling, cytoskeletal regulation, apoptosis, and vesicular trafficking pathways was identified across all enteric pathogens. Shigella exhibited unique interactions related to actin polymerization and immune suppression. Salmonella demonstrated distinct interactions with vesicle trafficking and intracellular survival pathways absent in E. coli. Vibrio species displayed specific interactions affecting epithelial barrier integrity and ion transport. Significant inter-species variations were observed within Salmonella and Vibrio strains. Conclusion: The study highlights a shared core of host interaction strategies among enteric pathogens, alongside pathogen-specific adaptations that underlie distinct disease phenotypes. These findings provide a systems-level understanding of enteric bacterial pathogenesis and identify potential targets for broad-spectrum and pathogen-specific therapeutic interventions.