Differences in Cryptococcus neoformans capsular polysaccharide structure influence assembly of alternative complement pathway C3 convertase on fungal surfaces.
Binding of complement component C3 and Factor B to Cryptococcus neoformans serotypes A through D via the alternative complement pathway was measured in a system containing fresh nonimmune human serum. Serotypes B and C (C. neoformans var. gattii) bound approximately half as many molecules of both complement components as serotypes A and D (C. neoformans var. neoformans). In contrast, removal of xylosyl and glucuronyl side chains from the mannan main chain of capsular polysaccharide by the Smith degradation procedure resulted in binding of similar quantities of C3 to each of the four serotypes. We conclude that the relatively high degree of side chain substitution of capsular polysaccharide from C. neoformans variety gattii contributes to inefficient surface assembly of the alternative pathway C3 convertase. Inefficient binding of alternative pathway complement components to serotypes B and C may contribute to the relative difficulty in successfully treating infections caused by these organisms.
Washburn
R G
RG
Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, NC 27103.
Bryant-Varela
B J
BJ
Julian
N C
NC
Bennett
J E
JE
D000107:Acetylation; D000946:Antigens, Fungal / Q000737:chemistry / Q000276:immunology*; D003176:Complement C3 / Q000378:metabolism*; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D011415:Complement Factor B / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D003455:Cryptococcus neoformans / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology*; D012703:Serotyping; D013172:Spores, Fungal / Q000276:immunology; D013329:Structure-Activity Relationship
D000946:Antigens, Fungal; D003176:Complement C3; D011134:Polysaccharides; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B