A surface lipoprotein on Pasteurella multocida binds complement factor I to promote immune evasion

Area of Science:

• Immunology
• Microbiology
• Structural Biology

Background:

• Pasteurella multocida is a significant cause of human wound infections and severe diseases in cattle.
• A subunit vaccine using the surface lipoprotein PmSLP has shown promise in protecting cattle.

Purpose of the Study:

• To investigate the immune evasion mechanisms of Pasteurella multocida involving the PmSLP protein.
• To elucidate the structural basis of PmSLP's interaction with host complement factor I (FI).

Main Methods:

• Co-immunoprecipitation assays to confirm binding of PmSLP to complement factor I (FI).
• Biochemical assays to assess the cleavage of complement components C3b and C4b by FI.
• Cryo-electron microscopy (Cryo-EM) to determine the structure of the PmSLP-FI complex.

Main Results:

• PmSLP directly binds to host complement factor I (FI).
• PmSLP facilitates cofactor-independent cleavage of C3b and C4b, components of all complement pathways.
• The cryo-EM structure reveals PmSLP stabilizes the catalytic domain of FI, enhancing its enzymatic activity.
• This represents the first identified bacterial protein that directly activates FI, targeting the entire complement cascade.

Conclusions:

• PmSLP is a novel bacterial immune evasion factor that directly activates complement factor I.
• This mechanism allows Pasteurella multocida to effectively evade host complement-mediated immunity.
• Understanding this interaction opens new avenues for developing therapeutics against P. multocida infections.