Molecular insights into drug repurposing and drug target proteins identification for Yersinia enterocolitica

Infectious diseases caused by bacteria such as Yersinia enterocolitica pose significant global health challenges. Y. enterocolitica, a Gram-negative bacterium, is known for causing gastrointestinal diseases in humans. The objective of this study was to identify potential drug targets to combat Y. enterocolitica infections.

A pan-genome analysis of 22 complete genomes of Yersinia enterocolitica was combined with subtractive genomics to identify potential drug targets. VacSol was used to screen for non-host homologous proteins, and essential proteins were identified using the Database of Essential Genes (DEG). Cytoplasmic proteins were selected based on predicted subcellular localization, modeled using SWISS-MODEL, and refined using GalaxyRefine. Their potential interactions with 30 fluoroquinolone compounds were evaluated through molecular docking using AutoDock Vina and MD simulation through GROMACS was performed.

The analysis identified 3,025 core genes, 2,267 non-host homologous proteins, and 29 essential proteins. Nine cytoplasmic proteins were selected for structural modeling and docking. Promising predicted interactions included the two-component response regulator OmpR with ciprofloxacin, large ribosomal subunit protein uL13 with nalidixic acid, phosphoheptose isomerase with norfloxacin, and protein-export protein SecB with ciprofloxacin.

These findings indicated that these proteins are viable targets for drug development against Y. enterocolitica. The increasing antibiotic resistance of Y. enterocolitica highlights the urgent need for novel therapeutic strategies, making these insights crucial for future drug development.