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Molecular Mimicry of Host Structures by Lipooligosaccharides of Neisseria Meningitidis: Characterization of Sialylated and Nonsialylated Lacto-N-Neotetraose (Galß1-4GlcNAcß1-3Galβ1-4Glc) Structures in Lipooligosaccharides Using Monoclonal Antibodies and Specific Lectins

  • Chao-Ming Tsai
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 491)

Abstract

Neisseria meningitidis lipooligosaccharides (LOSs) are classified into 12 immunotypes. Most LOSs are heterogeneous in having a few components by SDS-PAGE analysis that differ antigenic ally and chemically. We have utilized a monoclonal antibody that recognizes lacto-N-neotetraose (LNnT) and the lectin, Maackia amurensis leukoagglutinin (MAL), which is specific for NeuNAcα2-3GalβI-4GlcNAc trisacchride sequence to characterize the 12 N. meningitidis LOSs. Using the combination of ELISA, SDS-PAGE, Western blotting, and other chemical analyses, we have shown that the LNnT (Galβ1–4GlcNAcβ1–3Galβl–4Glc) sequence was present in the 4.0-kDa LOS components of seven immunotype LOSs seen on SDS-P AGE. Six of the seven LNnT -containing LOSs also bound the MAL lectin indicating that N-acetylneuraminic acid (NeuNAc) was α2,3-linked to the LNnT sequence in the LOSs. Sialylation of the terminal Gal of LNnT-containing 4.0-kDa component caused only a slight increase in its apparent MW to 4100 on SDS-P AGE. The one LOS with the LNnT-containing component, but not MAL-binding, was from a Group AN. meningitidis, which does not synthesize CMP-NeuNAc, the substrate needed for LOS sialylation. Thus, it is concluded (1) a common LNnT sequence is present in seven immunotype LOSs in addition to their immunotype epitopes, and (2) NeuNAc is α2->3 linked to the terminal Gal of LNnT if a organism synthesizes CMP-NeuNAc such as Groups Band C organisms. The above conclusions are consistent with the published structures of N. meningitidis LOSs. The results also demonstrate that specific carbohydrate-binding lectins and monoclonal antibodies can be used as simple yet effective tools to characterize specific carbohydrate sequences in a bacterial LOS or LPS such as N. meningitidis LOS.

It is intriguing that N. meningitidis LOSs mimiC certain glycosphingolipids, such as paragloboside (LNnT -cerami de) and sialylparagloboside, and some glycoproteins of the host in having LNnT and N-acetyllactosamine sequences respectively with or without α2->3 linked NeuNAc. Epidemiological studies of N. meningitidis suggest that the molecular mimicry of host structures by its LOS plays a role in the pathogenesis of N. meningitidis by helping the organism to evade host immune defenses in man. The molecular mimicry of host structures by LOS or LPS is also found in other human pathogens such as N. gonorrhoeae, Haemophilus ducreyi, H. injluenaze, Moraxella catarrhalis, Campylobacter jejuni, and Helicobacter pylori.

Keywords

Sialic Acid Neisseria Gonorrhoeae Capsular Polysaccharide Molecular Mimicry Meningococcal Disease 
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© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Chao-Ming Tsai
    • 1
  1. 1.Division of Bacterial ProductsCenter for Biologics Evaluation and Research, FDABethesdaUSA

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