Capsular sialic acid limits C5a production on type III group B streptococci

The majority of type III group B streptococcus (GBS) human neonatal infecti ons are caused by a genetically related subgroup called III-3. We have prop osed that a bacterial enzyme, C5a-ase, contributes to the pathogenesis of n eonatal infections with GBS by rapidly inactivating C5a, a potent pro-infla mmatory molecule, but many III-3 strains do not express C5a-ase. The amount of C5a produced in serum following incubation with representative type III strains was quantitated in order to better understand the relationship bet ween C5a production and C5a-ase expression. C5a production following incuba tion of bacteria with serum depleted of antibody to the bacterial surface w as inversely proportional to the sialic acid content of the bacterial capsu le, with the more heavily sialylated III-3 strains generating less C5a than the less-virulent, less-sialylated III-2 strains. The amount of C5a produc ed correlated significantly with C3 deposition on each bacterial strain. Re pletion with type-specific antibody caused increased C3b deposition and C5a production through alternative pathway activation, but C5a was functionall y inactivated by strains that expressed C5a-ase. The increased virulence of III-3 strains compared to that of III-2 strains results at least partially from the higher sialic acid content of III-3 strains, which inhibits both opsonophagocytic killing and C5a production in the absence of type-specific antibody. We propose that C5a-ase is not necessary for III-3 strains to ca use invasive disease because the high sialic acid content of III-3 strains inhibits C5a production.