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Capsular Sialic Acid Limits C5a Production on Type III Group B Streptococci

机译：荚膜唾液酸限制III型B组链球菌产生C5a

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The majority of type III group B streptococcus (GBS) human neonatal infections are caused by a genetically related subgroup called III-3. We have proposed that a bacterial enzyme, C5a-ase, contributes to the pathogenesis of neonatal infections with GBS by rapidly inactivating C5a, a potent pro-inflammatory 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 between C5a production and C5a-ase expression. C5a production following incubation of bacteria with serum depleted of antibody to the bacterial surface was inversely proportional to the sialic acid content of the bacterial capsule, with the more heavily sialylated III-3 strains generating less C5a than the less-virulent, less-sialylated III-2 strains. The amount of C5a produced correlated significantly with C3 deposition on each bacterial strain. Repletion with type-specific antibody caused increased C3b deposition and C5a production through alternative pathway activation, but C5a was functionally 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 cause invasive disease because the high sialic acid content of III-3 strains inhibits C5a production.
机译：大多数III型B组链球菌（GBS）人类新生儿感染是由称为III-3的遗传相关亚组引起的。我们已经提出，细菌酶C5a-酶通过快速灭活有效的促炎分子C5a来促进GBS新生儿感染的发病，但是许多III-3菌株不表达C5a-酶。与代表性的III型菌株孵育后，对血清中产生的C5a的量进行定量，以便更好地了解C5a产生与C5a酶表达之间的关系。在细菌与抗体表面缺乏抗体的血清一起孵育后，C5a的产生与细菌囊中唾液酸含量成反比，唾液酸化程度较高的III-3菌株产生的C5a比毒性​​低，唾液酸化程度较低的III少-2株。产生的C5a的量与每个细菌菌株上的C3沉积显着相关。类型特异性抗体的补充通过替代途径激活引起C3b沉积增加和C5a产生增加，但是C5a在功能上被表达C5a酶的菌株灭活。与III-2株相比，III-3株的毒力增加至少部分是由于III-3株的唾液酸含量较高，在没有类型特异性抗体的情况下，它抑制了调理吞噬细胞的杀伤作用和C5a的产生。我们建议C5a-酶对于III-3株引起侵袭性疾病不是必需的，因为III-3株的唾液酸含量高会抑制C5a的产生。

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