SIALYLATION OF NEISSERIA-MENINGITIDIS LIPOOLIGOSACCHARIDE INHIBITS SERUM BACTERICIDAL ACTIVITY BY MASKING LACTO-N-NEOTETRAOSE

Exogenous sialylation of gonococcal lipooligosaccharide causes resista nce to serum bactericidal activity. The aim of this study was to deter mine how lipooligosaccharide sialylation affects the serum sensitiviti es of group C Neisseria meningitidis Strains. The relationship between the degree of sialylation or expression of the lipooligosaccharide si alic acid acceptor, lacto-N-neotetraos (LNnT), of nine meningococcal s trains and their sensitivities to a pool of normal human sera was asse ssed. All strains expressed LNnT that was variously endogenously sialy lated. Susceptibility to serum bactericidal activity ranged from extre mely 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 w hen they were grown in medium that contained cytidine monophospho-N'ac etylneuraminic acid. Exogenous sialylation reduced the expression of f ree LNnT and significantly increased serum resistance. Exogenous sialy lation affected killing through both classical and alternative complem ent pathways. The killing of exogenously sialylated strains also corre lated with the amount of free LNnT. The amounts of endogenous, exogeno us, and total sialic acid bound to LNnT did not correlate with the res istance of strains to serum bactericidal activity; rather, the loss of free LNnT expression by sialylation was associated with resistance. I n conclusion, the expression of free LNnT by group C meningococcal str ains 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.