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C4bp binding to porin mediates stable serum resistance of Neisseria gonorrhoeae

conference contribution
posted on 16.02.2021, 05:33 by S Ram, Meabh CullinaneMeabh Cullinane, AM Blom, S Gulati, DP McQuillen, R Boden, BG Monks, C O'Connell, C Elkins, MK Pangburn, B Dahlbäck, PA Rice
Screening of 29 strains of Neisseria gonorrhoeae revealed that 16/21 serum resistant strains and 0/8 serum sensitive strains bound C4bp, suggesting that C4bp binding to gonococci could contribute to serum resistance. C4bp bound to gonococci retained cofactor (C4b-degrading) function. Using allelic exchange to construct strains with hybrid Por1A/B molecules, we demonstrate that the N-terminal loop (loop 1) of Por1A is required for C4bp binding. Serum resistant Por1B gonococcal strains also bind C4bp via their Por molecule. Using allelic exchange and site-directed mutagenesis, we have shown that loops 5 and 7 together form a negatively charged C4bp binding domain. C4bp-Por1B interactions are ionic in nature (inhibited by high salt as well as by heparin), while the C4bp-Por1A bond is hydrophobic. mAbs directed against SCR1 of the α-chain of C4bp inhibit C4bp binding to both Por1A and Por1B. Furthermore, only recombinant C4bp mutant molecules that contain α-chain SCR1 bind both Por1A and Por1B gonococci, confirming that SCR1 contains Por binding sites. C4bp α-chain monomers do not bind strains with either Por molecule, suggesting that the polymeric form of C4bp is required for binding to gonococci. Inhibition of C4bp binding to serum resistant Por1A and Por1B strains in a serum bactericidal assay using fAb fragments against C4bp SCR1 results in complete killing at 30 min of otherwise fully serum resistant strains in only 10% normal serum, underscoring the role of C4bp in mediating gonococcal serum resistance. © 2001 Elsevier Science B.V.

History

Publication Date

19/03/2001

Proceedings

International Immunopharmacology

Publisher

ELSEVIER SCIENCE BV

Volume

1

Issue

3

Pagination

(p. 423-432)

ISSN

1567-5769

Name of conference

XVIIIth International Complement Workshop

Location

SNOWBIRD, UTAH

Starting Date

23/07/2000

Finshing Date

27/07/2000

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