AUTHOR=Ribeiro Sara , Alves Karine , Nourikyan Julien , Lavergne Jean-Pierre , de Bernard Simon , Buffat Laurent 

TITLE=Identifying potential novel widespread determinants of bacterial pathogenicity using phylogenetic-based orthology analysis

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1494490

DOI=10.3389/fmicb.2025.1494490

ISSN=1664-302X

ABSTRACT=IntroductionThe global rise in antibiotic resistance and emergence of new bacterial pathogens pose a significant threat to public health. Novel approaches to uncover potential novel diagnostic and therapeutic targets for these pathogens are needed.MethodsIn this study, we conducted a large-scale, phylogenetic-based orthology analysis (OA) to compare the proteomes of pathogenic to humans (HP) and non-pathogenic to humans (NHP) bacterial strains across 734 strains from 514 species and 91 families.ResultsUsing a dedicated workflow, we identified 4,383 hierarchical orthologous groups (HOGs) significantly associated with the HP label, many of which are linked to critical factors such as stress tolerance, metabolic versatility, and antibiotic resistance. Both known virulence factors (VFs) and potential novel widespread pathogenicity determinants were uncovered, supported by both statistical testing and complementary protein domain analysis.DiscussionBy integrating curated strain-level pathogenicity annotations from BacSPaD with phylogeny-based OA, we introduce a novel approach and provide a novel resource for bacterial pathogenicity research.