Enterococcal leucine-rich repeat-containing protein involved in virulence and host inflammatory response

Enterococcal leucine-rich repeat-containing protein involved in virulence and host inflammatory response
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DOI:
10.1128/iai.00279-07
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发表时间:
2007-09-01
影响因子:
3.1
通讯作者:
Serror, Pascale
Serror, Pascale
中科院分区:
医学2区
文献类型:
--
作者:
Brinster, Sophie;Posteraro, Brunella;Serror, Pascale

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粪肠球菌是一种重要的院内致病菌,对免疫功能低下或有严重基础疾病的患者具有较高的发病率和死亡率。粪肠球菌基因组编码许多可能参与毒力的表面暴露蛋白。这项工作描述了粪肠球菌中的第一个内分泌蛋白样蛋白ElrA的特征,该蛋白属于最近鉴定的WxL表面蛋白家族。ElrA含有用于输出的N-末端信号肽、可与宿主细胞相互作用的富含亮氨酸的重复结构域和与肽聚糖相互作用的C-末端WxL结构域。在小鼠腹膜炎模型中破坏e1 rA基因可显著减弱细菌毒力e1 rA缺失突变体还显示宿主巨噬细胞感染缺陷和体内白细胞介素-6反应降低。最后,在体内诱导e1 rA表达。总之,这些结果表明EIrA在E. faecalis在体内的感染过程,并建议该表面蛋白可能有助于E。通过刺激宿主的炎症反应来增强粪肠球菌的毒力。
Enterococcus faecalis is an important nosocomial pathogen associated with high morbidity and mortality for patients who are immuntocompromised or who have severe underlying diseases. TheE.faecalis genome encodes numerous surface-exposed proteins that may be involved in virulence. This work describes the characterization of the first internalin-like protein in E.faecalis, ElrA, belonging to the recently identified WxL family of surface proteins. ElrA contains an N-terminal signal peptide for export, a leucine-rich repeat domain that may interact with host cells, and a C-terminal WxL domain that interacts with the peptidoglycan. Disruption of the e1rA gene significantly attenuates bacterial virulence in a mouse peritonitis model. The e1rA deletion mutant also displays a defect in infection of host macrophages and a decreased interieukin-6 response in vivo. Finally, e1rA expression is induced in vivo. Altogether, these results demonstrate a role for EIrA in the E. faecalis infectious process in vivo and suggest that this surface protein may contribute to E. faecalis virulence by stimulating the host inflammatory response.