UMMS Affiliation

Division of Infectious Diseases and Immunology

Date

11-7-2007

Document Type

Article

Subjects

Bacterial Outer Membrane Proteins; Complement C3b; Complement C4b; Humans; Neisseria gonorrhoeae; Neisseria meningitidis; Porins; Protein Binding; Protein Isoforms

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Complement is a key arm of the innate immune defenses against the pathogenic neisseriae. We previously identified lipooligosaccharide on Neisseria meningitidis as an acceptor for complement C4b. Little is known about other neisserial targets for complement proteins C3 and C4, which covalently attach to bacterial surfaces and initiate opsonization and killing. In this study we demonstrate that Neisseria gonorrhoeae porin (Por) 1B selectively binds C4b via amide linkages and C3b via ester linkages. Using strains expressing hybrid Por1A/1B molecules, a region spanned by loops 4 and 5 of Por1B was identified as the preferred binding site for C4b. We also identified the opacity protein (Opa), a major adhesin of pathogenic neisseriae, as a target for C4b and C3b on both N. meningitidis and N. gonorrhoeae. Using N. gonorrhoeae variants that predominantly expressed individual Opa proteins, we found that all Opa proteins tested (A, B, C, D, E, F, and I) bound C4b and C3b via amide and ester linkages, respectively. Amide linkages with Por1B and Opa were confirmed using serum containing only the C4A isoform, which exclusively forms amide linkages with targets. While monomers and heterodimers of C4Ab were detected on bacterial targets, C4Bb appeared to preferentially participate in heterodimer (C5 convertase) formation. Our data provide another explanation for the enhanced serum sensitivity of Por1B-bearing gonococci. The binding of C3b and C4b to Opa provides a rationale for the recovery of predominantly "transparent" (Opa-negative) neisserial isolates from persons with invasive disease, where the bacteria encounter high levels of complement.

Rights and Permissions

Citation: Infect Immun. 2008 Jan;76(1):339-50. Epub 2007 Nov 5. Link to article on publisher's site

DOI of Published Version

10.1128/IAI.00613-07

Related Resources

Link to Article in PubMed

Journal Title

Infection and immunity

PubMed ID

17984207

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