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Genetic Polymorphisms of Group B Streptococcus scpB Alter Functional Activity of a Cell-Associated Peptidase That Inactivates C5a

机译:B组链球菌scpB的遗传多态性会改变细胞相关肽酶的功能活性,从而使C5a失活。

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摘要

Many group B Streptococcus agalactiae strains and other pathogenic streptococci express a cell-associated peptidase that inactivates C5a (C5a-ase), the major neutrophil chemoattractant produced by activation of the complement cascade. Type III group B streptococci (GBS) can be classified genotypically into three restriction digest pattern types. Functional C5a-ase activity of GBS correlates with this genetic typing; therefore, we sought to identify a genetic basis for this phenomenon. Southern hybridization confirms that all type III GBS contain scpB, the gene encoding GBS C5a-ase. GBS strains with high C5a-ase functional activity and those with no or very low activity both express immunoreactive C5a-ase. The scpB sequence of strain I30, which has high C5a-ase activity, is 98.2% homologous to the previously reported serotype II GBS scpB sequence. The scpB sequences of strains I25 and GW, which have low or no C5a-ase activity, are identical. The predicted I25 and GW C5a-ase proteins share a four-amino-acid deletion affecting the protease histidine active-site consensus motif. Recombinant I30 C5a-ase has good functional activity, whereas recombinant I25 C5a-ase has low activity. These data demonstrate that functional C5a-ase differences between type III GBS strains are attributable to a genetic polymorphism of scpB. The ubiquitous expression of C5a-ase, irrespective of functional activity, suggests that C5a-ase may have a second, as yet unidentified, function.
机译:许多B组无乳链球菌菌株和其他致病性链球菌均表达与细胞相关的肽酶,该酶使C5a(C5a-酶)失活,C5a是由补体级联反应产生的主要嗜中性白细胞趋化因子。 III型B组链球菌(GBS)可以按基因型分为三种限制性消化模式类型。 GBS的功能性C5a酶活性与此基因分型有关。因此,我们试图确定这种现象的遗传基础。 Southern杂交证实所有III型GBS都含有scpB,即编码GBS C5a酶的基因。具有高C5a酶功能活性的GBS菌株和不具有或非常低活性的GBS菌株均表达免疫反应性C5a酶。具有高C5a酶活性的菌株I30的scpB序列与先前报道的血清型II GBS scpB序列同源性为98.2%。具有低或没有C5a酶活性的菌株I25和GW的scpB序列是相同的。预测的I25和GW C5a-酶蛋白共有四个氨基酸缺失,影响蛋白酶组氨酸活性位点共有基序。重组I25 C5a-酶具有良好的功能活性,而重组I25 C5a-酶具有低活性。这些数据表明III型GBS菌株之间的功能性C5a酶差异可归因于scpB的遗传多态性。不管功能活性如何,C5a酶的普遍表达表明C5a酶可能具有第二个功能,但尚未确定。

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