Skip to main content
Article thumbnail
Location of Repository

A Novel Sialic Acid Binding Site on Factor H Mediates Serum Resistance of Sialylated Neisseria gonorrhoeae

By Sanjay Ram, Ajay K. Sharma, Scott D. Simpson, Sunita Gulati, Daniel P. McQuillen, Michael K. Pangburn and Peter A. Rice


Factor H (fH), a key alternative complement pathway regulator, is a cofactor for factor I–mediated cleavage of C3b. fH consists of 20 short consensus repeat (SCR) domains. Sialic acid binding domains have previously been localized to fH SCRs 6–10 and 13. To examine fH binding on a sialylated microbial surface, we grew Neisseria gonorrhoeae in the presence of 5′-cytidinemonophospho-N-acetylneuraminic acid, which sialylates lipooligosaccharide and converts to serum resistance gonococci previously sensitive to nonimmune serum killing. fH domains necessary for binding sialylated gonococci were determined by incubating organisms with recombinant human fH (rH) and nine mutant rH molecules (deletions spanning the entire fH molecule). rH and all mutant rH molecules that contained SCRs 16–20 bound to the sialylated strain; no mutant molecule bound to serum-sensitive nonsialylated organisms. Sialic acid was demonstrated to be the fH target by flow cytometry that showed a fourfold increase in fH binding that was reversed by neuraminidase-mediated cleavage of sialic acid off gonococci. Functional specificity of fH was confirmed by decreased total C3 binding and almost complete conversion to iC3b on sialylated gonococci. Sialic acid can therefore bind fH uniquely through SCRs 16–20. This blocks complement pathway activation for N. gonorrhoeae at the level of C3

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (1984). A rapid, sensitive method for detection of alkaline phosphatase–conjugated anti-antibody on Western blots.
  2. (1977). Activation of the alternative complement pathway due to resistance of zymosanbound amplification convertase to endogenous regulatory mechanisms.
  3. (1988). Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H.
  4. (1977). Asymptomatic gonorrhea in men: caused by gonococci with unique nutritional requirements.
  5. (1989). Ba and Bb fragments of factor B activation: fragment production, biological activities, neoepitope expression and quantitation in clinical samples. Complement Inflammation.
  6. (1987). Bacterial sialic acid modulates activation of the alternative complement pathway of channel catfish (Ictalurus punctatus).
  7. (1994). Biologically active recombinant human complement factor H: synthesis and secretion by the baculovirus system.
  8. (1988). C3b receptor activity on transfected cells expressing glycoprotein C of herpes simplex virus types 1 and 2.
  9. (1982). Capsular sialic acid prevents activation of the alternative complement pathway by type III,
  10. (1977). Characterization of gonococcal antigens responsible for induction of bactericidal antibody in disseminated infection.
  11. (1987). Characterization of three monoclonal antibodies against C3 with selective specificities.
  12. (1981). Clinical manifestations of disseminated infection caused by Neisseria gonorrhoeae are linked to differences in bactericidal reactivity of infecting strains.
  13. (1996). Cloning of the lipooligosaccharide a-2,3-sialyltransferase from the bacterial pathogens Neisseria meningitidis and Neisseria gonor-751 Ram et al.
  14. (1978). Complement C3 convertase: cell surface restriction of b1H control and generation of restriction on neuraminidase-treated cells.
  15. (1997). Complement factor C3 deposition and serum resistance in isogenic capsule and lipooligosaccharide sialic acid mutants of serogroup B Neisseria meningitidis.
  16. (1994). Complement factor H and related proteins: an expanding family of complement-regulatory proteins?
  17. (1994). Complement-mediated bacterial killing assays.
  18. Control of the amplification convertase of complement by the plasma protein beta1H.
  19. (1988). Cytidine 59-monophospho-N-acetyl neuraminic acid and a low molecular weight factor from human blood cells induce lipopolysaccharide alteration in gonococci when conferring resistance to killing by human serum.
  20. (1988). Cytidine 59-monophospho-N-acetylneuraminic acid or a related compound is the low Mr factor from human red blood cells which induces gonococcal resistance to killing by human serum.
  21. (1990). Discrimination between activators and nonactivators of the alternative pathway of complement: regulation via a sialic acid/polyanion binding site on factor H.
  22. (1983). Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. Medicine
  23. (1992). Effect of exogenous sialylation of the lipooligosaccharide of Neisseria gonorrhoeae on opsonophagocytosis.
  24. (1988). Effect of gangliosides on activation of the alternative pathway of human complement.
  25. (1996). Efficient destruction of human immunodeficiency virus in human serum by inhibiting the protective action of complement factor H and decay accelerating factor (DAF,
  26. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
  27. Epstein-Barr virus regulates activation and processing of the third component of complement.
  28. (1981). Factors affecting the induction of phenotypically determined serum resistance of Neisseria gonorrhoeae grown in media containing serum or its diffusible components.
  29. (1984). Fractionation of guinea pig serum for an inducer of gonococcal resistance to killing by human serum: active fractions containing glucopeptides similar to those from human red blood cells.
  30. (1984). Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells.
  31. (1986). Glycoprotein C of herpes simplex virus 1 is an inhibitor of the complement cascade.
  32. Gonococcal lipooligosaccharide sialylation prevents752 Novel Sialic Acid Binding Region in Factor H for Sialylated Gonococci complement-dependent killing by immune sera.
  33. (1976). Gonococci causing disseminated gonococcal infection are resistant to the bactericidal action of normal human sera.
  34. (1970). Gonococci in urethral exudates possess a virulence factor lost on subculture.
  35. (1992). Growth of Neisseria gonorrhoeae in CMP-N-acetylneuraminic acid inhibits nonopsonic (opacity-associated outer membrane protein–mediated) interactions with human neutrophils.
  36. (1987). Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity.
  37. (1995). HIV glycoprotein 41 and complement factor H interact with each other and share functional as well as antigenic homology.
  38. (1981). Host modification of Sindbis virus sialic acid content influences alternative complement pathway activation and virus clearance.
  39. (1979). Human alternative complement pathway: membrane-associated sialic acid regulates the competition between B and beta1 H for cell-bound C3b.
  40. Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein b1H for cleavage of C3b and C4b in solution.
  41. Human complement proteins C3b, C4b, factor H and properdin react with specific sites
  42. (1996). Identification of a heparin binding domain in the seventh short consensus repeat of complement factor
  43. (1988). Identification of distinct C3b and C4b recognition sites in the human C3b/C4b receptor (CR1, CD35) by deletion mutagenesis.
  44. (1996). Identification of three physically and functionally distinct binding sites for C3b in human complement factor H by deletion mutagenesis.
  45. (1990). In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation.
  46. (1981). Induction of phenotypically determined resistance of Neisseria gonorrhoeae to human serum by factors in human serum.
  47. (1988). Inhibition of the alternative pathway of human complement by structural analogues of sialic acid.
  48. (1990). Inhibition of the complement cascade by the major secretory protein of vaccinia virus.
  49. (1995). Interaction of several complement proteins with gp120 and gp41, the two envelope glycoproteins of HIV-1.
  50. (1988). Lipooligosaccharides: the principal glycolipids of the neisserial outer membrane.
  51. (1986). Lipopolysaccharide alteration is associated with induced resistance of Neisseria gonorrhoeae to killing by human serum.
  52. (1995). Lo-750 Novel Sialic Acid Binding Region in Factor H for Sialylated Gonococci cation of the complement factor H binding site on streptococcal M6 protein.
  53. (1997). Localization by site-directed mutagenesis of the site in human complement factor H that binds to Streptococcus pyogenes M protein.
  54. (1991). Localization of the heparin-binding site on complement factor H.
  55. (1995). Mapping of the complement regulatory domains in the human factor H–like protein 1 and in factor H1.
  56. Modification by sialic acid of Neisseria gonorrhoeae lipooligosaccharide epitope expression in human urethral exudates: an immunoelectron microscopic analysis.
  57. (1976). Modulation of the alternative complement pathways by b 1 H globulin.
  58. (1989). Molecular basis for serum resistance in Neisseria gonorrhoeae.
  59. (1981). Monoclonal antibody analysis of lipopolysaccharide from Neisseria gonorrhoeae and Neisseria meningitidis.
  60. Monoclonal antibody that recognizes an outer membrane antigen common to the pathogenic Neisseria species but not to most nonpathogenic Neisseria species.
  61. (1983). Natural immunity to Sindbis virus is influenced by host tissue sialic acid content.
  62. (1980). Natural serum bactericidal activity against Neisseria gonorrhoeae isolates from disseminated, locally invasive, and uncomplicated disease.
  63. (1979). Phenotypically determined resistance of Neisseria gonorrhoeae to normal human serum: environmental factors in subcutaneous chambers in guinea pigs.
  64. (1988). Protein changes associated with induced resistance of Neisseria gonorrhoeae to killing by human serum are relatively minor.
  65. (1984). Red blood cells, a source of factors which induce Neisseria gonorrhoeae to resistance to complement-mediated killing by human serum.
  66. (1978). Regulation by membrane sialic acid of beta1H-dependent decay-dissociation of amplification C3 convertase of the alternative complement pathway.
  67. (1994). Regulation of alternative pathway complement activation by glycosaminoglycans: specificity of the polyanion binding site on factor H.
  68. (1994). Role of sialic acid in the resistance of Trypanosoma cruzi trypomastigotes to complement.
  69. (1993). Role of the YadA protein in prevention of opsonization of Yersinia enterocolitica by C3b molecules.
  70. (1992). Sialylation and human neutrophil killing of group C Neisseria meningitidis.
  71. (1985). Species specificity of recognition by the alternative pathway of complement.
  72. (1987). Specificity of antibodies against Neisseria gonorrhoeae that stimulate neutrophil chemotaxis.
  73. (1988). The complete amino acid sequence of human complement
  74. (1992). The serum resistance of gonococci in the majority of urethral exudates is due to sialylated lipopolysaccharide seen as a surface coat.
  75. (1991). The surface structure seen on gonococci after treatment with CMP-NANA is due to sialylation of surface lipopolysaccharide previously described as a ‘capsule.’
  76. (1992). Ultrastructures and interactions of complement factors
  77. (1988). Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins.
  78. (1989). Vaccinia virus encodes two proteins that are structurally related to members of the plasma serine protease inhibitor superfamily.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.