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

Area of Science:

• Bacteriology
• Immunology
• Structural Biology

Background:

• Pasteurella multocida is a significant pathogen causing wound infections in humans and severe diseases in cattle.
• A subunit vaccine using the surface lipoprotein PmSLP has shown promise for cattle protection.
• Understanding bacterial immune evasion mechanisms is crucial for developing effective treatments and vaccines.

Purpose of the Study:

• To investigate the mechanism by which Pasteurella multocida evades the host immune system.
• To elucidate the interaction between the bacterial surface lipoprotein PmSLP and host complement factor I (FI).
• To determine the structural basis for PmSLP-mediated complement evasion.

Main Methods:

• Biochemical assays to study the interaction between PmSLP and complement factor I (FI).
• Complement component cleavage assays to assess FI activity.
• Cryo-electron microscopy (Cryo-EM) to determine the structure of PmSLP bound to FI.

Main Results:

• The Pasteurella multocida surface lipoprotein PmSLP directly binds and activates host complement factor I (FI).
• PmSLP facilitates the cleavage of complement components C3b and C4b independently of cofactors, thereby inhibiting complement activation.
• 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 all complement pathways.

Conclusions:

• Pasteurella multocida employs a novel immune evasion strategy by hijacking complement factor I through its surface lipoprotein PmSLP.
• This mechanism allows the bacterium to evade the complement system, a critical component of innate immunity.
• The findings provide insights into pathogen-host interactions and potential targets for therapeutic interventions against Pasteurella multocida infections.