RrgA is a pilus-associated adhesin in Streptococcus pneumoniae.

RrgA is a pilus-associated adhesin in Streptococcus pneumoniae.
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DOI:
10.1111/j.1365-2958.2007.05908.x
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发表时间:
2007-10
影响因子:
3.6
通讯作者:
Henriques-Normark B
Henriques-Normark B
中科院分区:
生物学2区
文献类型:
--
作者:
Nelson AL;Ries J;Bagnoli F;Dahlberg S;Fälker S;Rounioja S;Tschöp J;Morfeldt E;Ferlenghi I;Hilleringmann M;Holden DW;Rappuoli R;Normark S;Barocchi MA;Henriques-Normark B

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粘附到宿主细胞在粘膜表面的微生物定殖中是重要的,并且肺炎链球菌粘附通过由三个亚基RrgA、RrgB和RrgC组成的细胞外菌毛的表达而显著增强。我们试图确定哪一个亚单位赋予粘附性。RrgA缺陷的细菌粘附性显著低于野生型生物体,而RrgA的过表达增强粘附性。重组单体RrgA与呼吸道细胞结合,RrgC与呼吸道细胞结合的亲和力较低,用RrgA预孵育上皮细胞可减少野生型有毛肺炎球菌的粘附。非粘附性RrgA阴性、RrgB和RrgC阳性微生物产生皮利,表明菌毛介导的粘附是由于RrgA的表达,而不是菌毛骨架本身。与此相反,RrgA阳性菌株破坏rrgB和rrgC基因表现出野生型的粘附,尽管未能产生皮利通过蛋白质印迹或免疫电镜。与野生型相比,接种有菌毛的RrgA阴性肺炎球菌的小鼠的上呼吸道细菌定殖密度显著更低;相反,表达非聚合RrgA的无菌毛肺炎球菌在鼻咽中的细菌数量与有菌毛的野生型细菌相似。这些数据表明,RrgA是中心的菌毛介导的粘附和疾病,即使在没有聚合菌毛生产。
Adherence to host cells is important in microbial colonization of a mucosal surface, and Streptococcus pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits, RrgA, RrgB and RrgC. We sought to determine which subunit(s) confers adherence. Bacteria deficient in RrgA are significantly less adherent than wild-type organisms, while overexpression of RrgA enhances adherence. Recombinant monomeric RrgA binds to respiratory cells, as does RrgC with less affinity, and pre-incubation of epithelial cells with RrgA reduces adherence of wild-type piliated pneumococci. Non-adherent RrgA-negative, RrgB- and RrgC-positive organisms produce pili, suggesting that pilus-mediated adherence is due to expression of RrgA, rather than the pilus backbone itself. In contrast, RrgA-positive strains with disrupted rrgB and rrgC genes exhibit wild-type adherence despite failure to produce pili by Western blot or immunoelectron microscopy. The density of bacteria colonizing the upper respiratory tract of mice inoculated with piliated RrgA-negative pneumococci was significantly less compared with wild-type; in contrast, non-piliated pneumococci expressing non-polymeric RrgA had similar numbers of bacteria in the nasopharynx as piliated wild-type bacteria. These data suggest that RrgA is central in pilus-mediated adherence and disease, even in the absence of polymeric pilus production.
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