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

Lewis, Lisa A.; Ram, Sanjay; Prasad, Alpana; Gulati, Sunita; Getzlaff, Silke; Blom, Anna LU ; Vogel, Ulrich and Rice, Peter A. (2008) In Infection and Immunity 76(1). p.339-350
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 N. 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... (More)
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 N. 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 predominately expressed individual Opa proteins, we found that all expressed 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 enhanced serum sensitivity of Por1B-bearing gonococci. The binding of C3b and C4b to Opa provide 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
76
issue
1
pages
339 - 350
publisher
American Society for Microbiology
external identifiers
  • pmid:17984207
  • wos:000252126000037
  • scopus:37749005256
ISSN
1098-5522
DOI
10.1128/IAI.00613-07
language
English
LU publication?
yes
id
1dbd9e1a-a39d-4e2d-83dc-a5669befaaf7 (old id 1138702)
date added to LUP
2008-04-29 09:13:37
date last changed
2017-10-22 04:51:43
@article{1dbd9e1a-a39d-4e2d-83dc-a5669befaaf7,
  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 N. 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 predominately expressed individual Opa proteins, we found that all expressed 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 enhanced serum sensitivity of Por1B-bearing gonococci. The binding of C3b and C4b to Opa provide 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.},
  author       = {Lewis, Lisa A. and Ram, Sanjay and Prasad, Alpana and Gulati, Sunita and Getzlaff, Silke and Blom, Anna and Vogel, Ulrich and Rice, Peter A.},
  issn         = {1098-5522},
  language     = {eng},
  number       = {1},
  pages        = {339--350},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Defining targets for complement components C4b and C3b on the pathogenic neisseriae},
  url          = {http://dx.doi.org/10.1128/IAI.00613-07},
  volume       = {76},
  year         = {2008},
}