E-cadherin is a receptor for the common protein pneumococcal surface adhesin A (PsaA) of Streptococcus pneumoniae

E-cadherin is a receptor for the common protein pneumococcal surface adhesin A (PsaA) of Streptococcus pneumoniae
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DOI:
10.1016/j.micpath.2007.02.003
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发表时间:
2007-05-01
影响因子:
3.8
通讯作者:
Ades, Edwin W.
Ades, Edwin W.
中科院分区:
医学3区
文献类型:
--
作者:
Anderton, Julie M.;Rajam, Gowrisankar;Ades, Edwin W.

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肺炎链球菌(Pnc)通过细菌粘附素在鼻咽部携带和定植的第一步中与鼻咽部(NP)上皮细胞结合。肺炎球菌表面粘附素A(PsaA)在肺炎球菌粘附和定植中起重要作用。鉴定PsaA在人类上皮细胞上的受体将有助于理解这种细菌的发病机制。使用共价结合到荧光球(fluosphere)的重组PsaA,我们显示PsaA通过与人细胞受体E-钙粘蛋白的相互作用与NP细胞结合。SDS-PAGE银染色分析表明PsaA与E-钙粘蛋白结合。重组人E-钙粘蛋白结合并阻断PsaA包被的荧光球和整个透明细菌粘附于NP细胞,但不阻断Pnc PsaA(-)突变体。重组E-选择素和人041整联蛋白不结合或阻断PsaA包被的荧光球对NP细胞的粘附。同样,如果NP细胞与抗E-钙粘蛋白抗体预孵育,则PsaA包被的荧光球对细胞的粘附显著降低(46%,P = 0.05)。此外,当使用E-钙粘蛋白转染的细胞时,我们观察到PsaA包被的荧光球更有效地与表达E-钙粘蛋白的细胞结合。这项工作确定E-钙粘蛋白作为一个受体对人类上皮细胞的肺炎球菌表面粘附素,PsaA。(C)2007爱思唯尔有限公司保留所有权利。
Streptococcus pneumoniae (Pnc) binds to nasopharyngeal (NP) epithelial cells in the first steps of nasopharyngeal carriage and colonization through bacterial adhesins. The pneumococcal surface adhesin A (PsaA) has previously been reported to play a significant role in pneumococcal adherence and colonization. Identification of a receptor for PsaA on human epithelium will aid in understanding the pathogenesis of this bacterium. Using recombinant PsaA covalently bound to fluorescent spheres (fluospheres), we show PsaA binds to NP cells through interaction with the human cellular receptor, E-cadherin. SDS-PAGE silver stain analysis demonstrates binding of PsaA to E-cadherin. Recombinant human E-cadherin binds to and blocks PsaA-coated fluospheres and whole transparent bacteria from adhering to NP cells, but does not block a Pnc PsaA(-) mutant. Recombinant E-selectin and human 041 integrin did not bind to or block PsaA-coated fluosphere adherence to NP cells. Likewise, if NP cells were preincubated with anti-E-cadherin antibody, there was a significant decrease (46%, P = 0.05) in PsaA-coated fluosphere adherence to the cells. Additionally, when using E-cadherin transfected cells, we observed PsaA-coated fluospheres bind more efficiently to cells which express E-cadherin. This work identifies E-cadherin as a receptor on human epithelial cells for the pneumococcal surface adhesin, PsaA. (C) 2007 Elsevier Ltd. All rights reserved.