Sialylation of Neisseria meningitidis lipooligosaccharide inhibits serum bactericidal activity by masking lacto-N-neotetraose.
Exogenous sialylation of gonococcal lipooligosaccharide causes resistance to serum bactericidal activity. The aim of this study was to determine how lipooligosaccharide sialylation affects the serum sensitivities of group C Neisseria meningitidis strains. The relationship between the degree of sialylation or expression of the lipooligosaccharide sialic acid acceptor, lacto-N-neotetraose (LNnT), of nine meningococcal strains and their sensitivities to a pool of normal human sera was assessed. All strains expressed LNnT that was variously endogenously sialylated. Susceptibility to serum bactericidal activity ranged from extremely sensitive to resistant in 50% serum. For endogenously sialylated strains, the amount of killing correlated with the amount of free LNnT above a threshold of expression; strains that expressed less than the threshold survived in 25% serum. All strains added more sialic acid when they were grown in medium that contained cytidine monophospho-N-acetylneuraminic acid. Exogenous sialylation reduced the expression of free LNnT and significantly increased serum resistance. Exogenous sialylation affected killing through both classical and alternative complement pathways. The killing of exogenously sialylated strains also correlated with the amount of free LNnT. The amounts of endogenous, exogenous, and total sialic acid bound to LNnT did not correlate with the resistance of strains to serum bactericidal activity; rather, the loss of free LNnT expression by sialylation was associated with resistance. In conclusion, the expression of free LNnT by group C meningococcal strains is directly associated with the amount of killing of organisms in pooled human sera. Both endogenous and exogenous lipooligosaccharide sialylation are associated with increased serum resistance by masking LNnT.
Estabrook
M M
MM
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. mxe16@po.cwru.edu
Griffiss
J M
JM
Jarvis
G A
GA
D000907:Antibodies, Bacterial / Q000097:blood; D001770:Blood Bactericidal Activity; D003167:Complement Activation; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000276:immunology*; D009844:Oligosaccharides / Q000032:analysis
D000907:Antibodies, Bacterial; D008070:Lipopolysaccharides; D009844:Oligosaccharides; C023023:lipid-linked oligosaccharides; C013084:lacto-N-neotetraose; D019158:N-Acetylneuraminic Acid