PbsP, a cell wall-anchored protein that binds plasminogen to promote hematogenous dissemination of group B Streptococcus
PbsP, a cell wall-anchored protein that binds plasminogen to promote hematogenous dissemination of group B Streptococcus
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PbsP，一种细胞壁锚定蛋白，可结合纤溶酶原促进 B 族链球菌的血行传播
DOI：
10.1111/mmi.13357
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发表时间：
2016-07-01
影响因子：
3.6
通讯作者：
Beninati, Concetta
中科院分区：
文献类型：
--
作者：
Buscetta, Marco;Firon, Arnaud;Beninati, Concetta
无乳链球菌（B组链球菌或GBS）是新生儿侵袭性感染的主要原因，其毒力取决于其与细胞和宿主成分相互作用的能力。在这里，我们的特点是表面蛋白与GBS病理生理学的关键功能。这种粘附素，命名为PbsP，具有两个链球菌表面重复结构域，一个富含甲硫氨酸和赖氨酸的区域，和一个LPXTG细胞壁锚定基序。PbsP介导的纤溶酶原（Plg）的结合在体外和体内，我们表明，细胞表面结合的Plg可以激活成纤溶酶的组织纤溶酶原激活剂，以增加细菌的胞外蛋白水解活性。在感染的小鼠模型中，PbsP的缺乏导致穿过脑内皮细胞的细菌迁移减少和毒力受损。PbsP在主要GBS谱系中是保守的，并且是非CC17 GBS菌株中的主要纤溶酶原粘附素。重要的是，用重组PbsP免疫小鼠赋予保护性免疫。我们的研究结果表明，GBS已经发展出不同的策略来招募Plg，这表明获得细胞表面蛋白水解活性的能力对于这种细菌的侵袭性是必不可少的。
Streptococcus agalactiae (Group B Streptococcus or GBS) is a leading cause of invasive infections in neonates whose virulence is dependent on its ability to interact with cells and host components. We here characterized a surface protein with a critical function in GBS pathophysiology. This adhesin, designated PbsP, possesses two Streptococcal Surface Repeat domains, a methionine and lysine-rich region, and a LPXTG cell wall-anchoring motif. PbsP mediates plasminogen (Plg) binding both in vitro and in vivo and we showed that cell surface-bound Plg can be activated into plasmin by tissue plasminogen activator to increase the bacterial extracellular proteolytic activity. Absence of PbsP results in a decreased bacterial transmigration across brain endothelial cells and impaired virulence in a murine model of infection. PbsP is conserved among the main GBS lineages and is a major plasminogen adhesin in non-CC17 GBS strains. Importantly, immunization of mice with recombinant PbsP confers protective immunity. Our results indicate that GBS have evolved different strategies to recruit Plg which indicates that the ability to acquire cell surface proteolytic activity is essential for the invasiveness of this bacterium.