Phase-variation of the truncated lipo-oligosaccharide of Neisseria meningitidis NMB phosphoglucomutase isogenic mutant NMB-R6.
The detection of antibodies specific to meningococcal lipo-oligosaccharides (LOSs; outer-core-->inner-core-->lipid A) in sera of patients convalescent from meningococcal infection suggests the potential use of LOS as a vaccine to combat pathogenic Neisseria spp. Removal of the outer-core region, which expresses glycans homologous to human blood-group antigens, is a required first-step in order to avoid undesirable immunological reactions following vaccination. To this end, we describe here the structural makeup of the LOS produced by serogroup B N. meningitidis NMB isogenic phosphoglucomutase (Pgm) mutant (NMB-R6). The dominant LOS types produced by NMB-R6 expressed a deep-truncated inner-core region, GlcNAc-(1-->2)-LDHepII-(1-->3)-LDHepI-(1-->5)-[Kdo-2-->4]-Kdo-->lipid A, with one PEA unit attached at either O-6 or O-7 of LDHepII, or with two simultaneously PEA moieties attached at O-3 and O-6 or O-3 and O-7 of the same unit. Unexpectedly, this mutation did not completely deactivate the production of Glc, as some LOS molecules were observed to carry Glc at O-4 of LDHepI and at O-3 of LDHepII. A glycoconjugate vaccine comprised of NMB-R6 LOSs is currently being evaluated in our laboratory.
Monteiro
Mario A
MA
Wyeth Vaccines Research, 211 Bailey Road, West Henrietta, NY 14586, USA. monteiro@uoguelph.ca
Fortuna-Nevin
Maria
M
Farley
John
J
Pavliak
Viliam
V
D000117:Acetylglucosamine / Q000032:analysis; D002240:Carbohydrate Sequence; D002849:Chromatography, Gas; D004591:Electrophoresis, Polyacrylamide Gel; D004983:Ethanolamines / Q000032:analysis; D005690:Galactose / Q000032:analysis; D005947:Glucose / Q000032:analysis; D005958:Glucosephosphates / Q000378:metabolism; D006539:Heptoses / Q000032:analysis; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D038541:Neisseria meningitidis, Serogroup B / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D025942:Oligosaccharides, Branched-Chain / Q000737:chemistry; D010733:Phosphoglucomutase / Q000235:genetics* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013400:Sugar Acids / Q000032:analysis
D004983:Ethanolamines; D005958:Glucosephosphates; D006539:Heptoses; D008070:Lipopolysaccharides; D025942:Oligosaccharides, Branched-Chain; D013400:Sugar Acids; C023023:lipid-linked oligosaccharides; C002532:2-keto-3-deoxyoctonate; C026312:glycero-manno-heptose; C005448:phosphorylethanolamine; C031590:glucose-1-phosphate; D010733:Phosphoglucomutase; D005947:Glucose; D000117:Acetylglucosamine; D005690:Galactose