Pathogenic Neisseria Bind the Complement Protein CFHR5 via Outer Membrane Porins

Area of Science:

• Microbiology
• Immunology
• Complement System Biology

Background:

• Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens.
• These bacteria bind complement factor H (CFH), a key complement system regulator.
• Interactions with structurally similar CFH-related proteins (CFHRs) are poorly understood due to limited specific reagents.

Purpose of the Study:

• To investigate the binding of pathogenic Neisseria to CFHR proteins.
• To characterize the mechanism by which Neisseria interacts with CFHR5.
• To determine the functional consequences of Neisseria-CFHR5 interactions on complement activation.

Main Methods:

• Generation of a panel of monoclonal antibodies specific to CFHR proteins.
• Testing Neisseria binding to CFHR5 using these antibodies.
• Investigating the role of PorB and lipopolysaccharide in the interaction.
• Assessing complement activation on Neisseria gonorrhoeae surfaces.

Main Results:

• CFHR5 is bound by both pathogenic Neisseria species.
• CFHR5 binds to the PorB protein in the presence of sialylated lipopolysaccharide.
• This interaction enhances complement activation on the surface of Neisseria gonorrhoeae.
• Similar binding mechanisms were observed for Neisseria meningitidis and Neisseria gonorrhoeae.

Conclusions:

• CFHR5 is a novel binding target for pathogenic Neisseria.
• The PorB protein and sialylated lipopolysaccharide mediate CFHR5 binding.
• Neisseria-CFHR5 interactions can modulate complement activation, potentially impacting host defense evasion.
• This study provides new insights into bacterial evasion strategies within the complement system.