Comparative pangenomics of Pasteurella multocida uncovers adhesins specific to capsular serogroup B strains associated with bovine host tropism.

Haemorrhagic septicaemia (HS), an acute and highly fatal disease of bovines in tropical countries of Africa and Asia, including India, is primarily caused by Pasteurella multocida serogroup B:2 strains. Although P. multocida strains are ubiquitous and known to infect a wide range of host species with varied clinical manifestations hitherto, the molecular basis of host tropism remains unknown. In this study, we present an integrated genomic, structural, and molecular dynamics framework to investigate how P. multocida serogroup B strains selectively adhere to bovine tissues. Comparative pangenomic analysis identified 115 genes significantly enriched in serogroup B strains, among which five lineage-specific putative adhesins were predicted through a multi-layer computational pipeline. In silico adhesin-fibronectin docking and interface energetics analyses identified preferential binding of these five adhesins to bovine fibronectin FnIII 9–10 domains, with markedly weaker interactions observed for non-bovine (caprine, pig, chicken and rabbit) homologues. Molecular dynamics simulations further revealed exceptional structural stability and favourable binding energetics for three adhesins (PACFBAAN_02021, PACFBAAN_00422 and PACFBAAN_00429), whereas two adhesins (PACFBAAN_01225 and PACFBAAN_01232) exhibited substantially lower adhesive performance. Together, these adhesins represent a potential molecular signature of bovine host tropism and warrant experimental validation for diagnostics, anti-adhesion therapeutics, and subunit vaccine development.