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The Journal of experimental medicine
Mar 02, 1998;187 (5): 743-52.

A novel sialic acid binding site on factor H mediates serum resistance of sialylated Neisseria gonorrhoeae.

S Ram, A K Sharma, S D Simpson, S Gulati, D P McQuillen, M K Pangburn, P A Rice
Author Information
  1. S Ram: The Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, Massachusetts 02118, USA. sram@bu.edu
PMID: 9480984 DOI: 10.1084/jem.187.5.743

Abstract

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.

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Grants

  1. R01 AI032725/NIAID NIH HHS
  2. R37 AI032725/NIAID NIH HHS
  3. R56 AI032725/NIAID NIH HHS
  4. AI-32725/NIAID NIH HHS

MeSH Term

Antigens, Bacterial
Complement C3b
Complement Factor H
Gonorrhea
Humans
Lipopolysaccharides
Neisseria gonorrhoeae
Neuraminidase
Repetitive Sequences, Nucleic Acid
Sialic Acids

Chemicals

Antigens, Bacterial
CFH protein, human
Lipopolysaccharides
Sialic Acids
lipid-linked oligosaccharides
Complement C3b
Complement Factor H
Neuraminidase
Journal Article Research Support, U.S. Gov't, P.H.S.
Article has an altmetric score of 6

Word Cloud

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