NOVEL THERAPEUTIC PROTEIN TARGETS IDENTIFICATION IN ANAPLASMA PHAGOCYTOPHILUM IN POST-GENOMIC ERA

Abstract

Anaplasma phagocytophilum, a Gram-negative obligate intracellular bacterium causing human granulocytic anaplasmosis (HGA), necessitates the development of targeted interventions due to its non-specific clinical presentation and potential morbidity. This study utilized in-silico reverse vaccinology and subtractive genomics to identify conserved vaccine and drug targets across multiple A. phagocytophilum strains. Comparative genomic analysis of five A. phagocytophilum strains identified a core genome of 1007 genes. Subsequent non-host homology filtering against host genomes yielded 726 potential targets. Prioritization based on gene essentiality narrowed the selection to 21 candidates, which were further characterized for cellular localization, functionality, and structural properties via 3D modeling. Druggability assessment was performed on the modeled structures of conserved, essential, and non-host homologous proteins.In-silico screening revealed three promising targets: 30S ribosomal protein S10, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, and biotin synthase. These proteins exhibited high conservation across analyzed strains, demonstrated essentiality for bacterial viability, and lacked significant host homology. Structural modeling and druggability analysis suggest their potential as effective targets for novel drug and vaccine development against A. phagocytophilum.