Protective Antigen PlpE Mediates the Binding of Pasteurella multocida to Host Fibronectin

Pasteurella multocida is the primary etiological agent of pasteurellosis, which causes infectious diseases in a wide range of animals and humans. PlpE, a lipoprotein of P. multocida, serves as an important protective antigen of this pathogen, yet its pathogenic role remains largely unclear. In this study, we investigated the role of PlpE in the binding of P. multocida to two common host molecules, fibronectin (Fn) and plasminogen (Plg). The recombinant PlpE was prepared. Far Western blot and enzyme-linked immunosorbent assay (ELISA) were used to detect the binding activity of recombinant PlpE to Fn and Plg. PlpE-specific polyclonal antibodies were prepared, and its blocking effect was determined. Finally, AlphaFold was employed to elucidate the molecular mechanisms underlying the binding of PlpE to host molecules. Soluble recombinant PlpE was obtained with high purity. Far western blot assays showed that PlpE could bind to both Fn and Plg, while ELISA only detected a significant specific binding between PlpE and Fn. PlpE-specific polyclonal antibodies significantly inhibited the binding of P. multocida to Fn, but had no inhibitory effect on its binding to Plg. Structural analysis revealed that PlpE contains two distinct functional domains, and protein complex docking analysis demonstrated that PlpE can bind to multiple functional domains of Fn from humans and various animal species. In conclusion, the protective antigen PlpE mediates the adhesion of P. multocida to host Fn. This study deepens the understanding of the pathogenic role of PlpE and provides novel insights into the molecular mechanisms of PlpE-induced immunity.