Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis.
Group B and C Neisseria meningitidis are the major cause of meningococcal disease in the United States and in Europe. N . meningitidis lipooligosaccharide (LOS), a major surface antigen, can be divided into 12 immunotypes of which L1 through L8 were found among Group B and C organisms. Groups B and C but not Group A may sialylate their LOSs with N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis leukoagglutinin (MAL), which recognizes NeuNAcalpha2-3Galbeta1-4GlcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot analyses revealed that these six LOSs contained only the NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS components, which have a common terminal lacto-N-neotetraose (LNnT, Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown by previous studies. The LOS-lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves alpha2-->3 linked sialic acid. Methylation analysis of a representative LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide) and sialylparagloboside and some glycoproteins in having LNnT and N-acetyllactosamine sequences, respectively, with or without alpha2-->3 linked NeuNAc. The molecular mimicry of the LOSs may play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man.
Tsai
C M
CM
Division of Bacterial Products, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892, USA.
Chen
W H
WH
Balakonis
P A
PA
D000942:Antigens, Bacterial / Q000737:chemistry; D000954:Antigens, Surface / Q000737:chemistry; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D008745:Methylation; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000737:chemistry* / Q000276:immunology / Q000472:pathogenicity; D014774:Virulence / Q000276:immunology
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D037102:Lectins; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides