Capsular sialic acid prevents activation of the alternative complement pathway by type III, group B streptococci.

Abstract

Abstract The polysaccharide capsule of type III, group B Streptococcus (GBS), a repeating unit of five monosaccharides including terminal sialic acid residues has been shown previously not to activate the alternative complement pathway in the absence of type-specific antibody. Data from 13C nuclear magnetic resonance studies indicate that the carboxylate group of the terminal sialic acid associates with the backbone of the type III antigen producing a complex tertiary structure that is critical to the serologic specificity of the antigen. The present studies indicate that the carboxylate group of sialic acid, functioning either as a critical component of the sialic acid molecule or by rendering structural conformation or charge to type III, GBS antigen modulates the capacity of these organisms to activate the alternative pathway. Formalin-killed organisms were employed as particles to assess alternative pathway-mediated complement consumption by sera deficient in type-specific antibody: 1) native type III, GBS containing one sialic acid residue per antigenic repeating unit; 2) neuraminidase-cleaved type III, GBS; and 3) type III, GBS in which the carboxylate groups of sialic acid were reduced to hydroxymethyl groups, thereby altering the tertiary configuration while retaining 5-acetamido-3, 5-dideoxy-nonulose residues in a terminal position on the molecule. Control, fully sialated GBS failed to induce consumption of C3 and factor B in C2-deficient human serum and in serum with a low specific antibody concentration chelated with MgEGTA buffer. In contrast, neuraminidase-cleaved organisms induced 23 and 45% consumption of C3 and B, respectively, in C2-deficient serum and 43 and 47% consumption of C3 and B, respectively, in MgEGTA-chelated serum with a low-specific antibody concentration. Consumption of C3 and B by chemically reduced type III, GBS quantitatively and kinetically paralleled that observed for neuraminidase-treated organisms. The use of MgEGTA-chelated serum ruled out activation by the C1 bypass mechanism of complement activation. Finally, consumption of C3 and B was induced by neuraminidasecleaved and chemically reduced particles but not by control particles in the presence of agammaglobulinemia serum ruling out the participation of non-type-specific antibody in activating the alternative pathway. These data support the concept that the tertiary molecular conformation rendered to the capsule of type III GBS by the charge on the carboxylate group of sialic acid could be critical to the inhibition of the alternative pathway by sera deficient in specific antibody.