Reverse vaccinology-based identification of immunogenic membrane proteins from zoonotic multidrug-resistant Proteus vulgaris: a one health approach to cross-species vaccine development.

Abstract

BACKGROUND: Proteus vulgaris is a Gram-negative opportunistic bacterium implicated in wound infections, urinary tract infections, foodborne illnesses, pneumonia and septicemia. It poses a growing threat to human, veterinary and aquaculture health systems. In animals, P. vulgaris has been isolated from cattle, poultry, and pets, while in fish species such as Nile tilapia and Clarias gariepinus, it contributes to ulcerative and systemic diseases. Its frequent detection in raw milk, meat, and retail fish highlights its zoonotic potential. The rise of multidrug-resistant strains across clinical, veterinary, and food sectors underscores the urgent need for alternative control strategies. RESULTS: This study employed reverse vaccinology and immunoinformatics to identify potential vaccine targets against P. vulgaris. Candidate proteins were screened based on subcellular localization, antigenicity, allergenicity, toxicity, similarity to human proteins, B- and T-cell epitope binding, immune simulation results, conservation analysis and key physicochemical properties. Seven promising vaccine candidates were identified: Cytochrome bd-I oxidase subunit CydX (A0A094UCZ6), TatA translocase (A0A379F7E9), cytochrome o ubiquinol oxidase subunit IV (KGA56684), hydrogenase maturation factor (A0A379F868), bacteriophage Rz lysis family protein (KGA60362), a lipoprotein (A0A379F4X1) and a hypothetical protein (A0A379F5R5). These targets exhibited strong immunogenic potential, as indicated by immune simulation graphs showing pronounced IFN-γ responses and IgG production. CONCLUSION: The study supports vaccine development as a viable strategy to combat multidrug-resistant P. vulgaris across species. The identified targets offer promising leads for developing species-specific or cross-protective vaccines applicable in veterinary and aquaculture settings. By addressing veterinary, aquaculture and zoonotic concerns, this research contributes to integrated "One Health" solutions for antimicrobial resistance control and cross-species disease prevention.