Adherence of Streptococcus pneumoniae to respiratory epithelial cells is inhibited by sialylated oligosaccharides.
To study carbohydrate-mediated adherence of Streptococcus pneumoniae to the human airway, we measured binding of live S. pneumoniae organisms to a cultured cell line derived from the lining of the conjunctiva and to primary monolayers of human bronchial epithelial cells in the presence and absence of oligosaccharide inhibitors. Both encapsulated and nonencapsulated strains of S. pneumoniae grown to mid-logarithmic phase in suspension culture adhered to cultured primary respiratory epithelial cells and the conjunctival cell line. Adherence of nine clinically prevalent S. pneumoniae capsular types studied was inhibited preferentially by sialylated oligosaccharides that terminate with the disaccharide NeuAc alpha2-3(or 6)Galbeta1. Adherence of some strains also was weakly inhibited by oligosaccharides that terminate with lactosamine (Galbeta1-4GlcNAcbeta1). When sialylated oligosaccharides were covalently coupled to human serum albumin at a density of approximately 20 oligosaccharides per molecule of protein, the molar inhibitory potency of the oligosaccharide inhibitor was enhanced 500-fold. The above-mentioned experiments reveal a previously unreported dependence upon sialylated carbohydrate ligands for adherence of S. pneumoniae to human upper airway epithelial cells. Enhanced inhibitory potencies of polyvalent over monovalent forms of oligosaccharide inhibitors of adherence suggest that the putative adhesin(s) that recognizes the structure NeuAc alpha2-3(or 6)Galbeta1 is arranged on the bacterial surface in such a manner that it may be cross-linked by oligosaccharides covalently linked to human serum albumin.
Barthelson
R
R
Neose Technologies, Inc., Horsham, Pennsylvania 19044, USA. rbarthel@neose.com
Mobasseri
A
A
Zopf
D
D
Simon
P
P
D001422:Bacterial Adhesion / Q000187:drug effects*; D001980:Bronchi / Q000382:microbiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology; D009844:Oligosaccharides / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000502:physiology*
D009844:Oligosaccharides; D019158:N-Acetylneuraminic Acid