Defining targets for complement components C4b and C3b on the pathogenic neisseriae.

Area of Science:

• Immunology
• Microbiology
• Molecular Biology

Background:

• The complement system is crucial for innate immunity against pathogenic Neisseria species.
• Previous work identified lipooligosaccharide as a Neisseria meningitidis C4b acceptor.
• Limited knowledge exists on Neisseria targets for complement proteins C3 and C4.

Purpose of the Study:

• To identify neisserial targets for complement proteins C3 and C4.
• To elucidate the binding mechanisms and locations of complement proteins on Neisseria.
• To understand the role of complement interactions in Neisseria pathogenesis.

Main Methods:

• Investigated binding of C4b and C3b to Neisseria gonorrhoeae porin (Por) 1B using hybrid Por1A/1B molecules.
• Identified opacity (Opa) proteins as targets for C4b and C3b on both N. meningitidis and N. gonorrhoeae.
• Utilized C4A isoform-containing serum to confirm amide linkages and analyzed complement component interactions.

Main Results:

• Neisseria gonorrhoeae Por1B binds C4b via amide linkages and C3b via ester linkages, with loops 4 and 5 being key binding sites for C4b.
• All tested Opa proteins (A, B, C, D, E, F, I) bind C4b and C3b through amide and ester linkages, respectively.
• C4b binding to Por1B and Opa explains enhanced serum sensitivity of Por1B-expressing gonococci and suggests Opa-negative isolates are favored in invasive disease.

Conclusions:

• Porin 1B and Opa proteins are significant targets for complement C3b and C4b on pathogenic Neisseria.
• Specific binding linkages (amide for C4b, ester for C3b) and protein regions are identified.
• Complement interactions with Por1B and Opa influence Neisseria survival and disease tropism, favoring Opa-negative variants in invasive infections.