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Inv1:迟钝爱德华氏菌的一种侵袭因子和一种保护性免疫原,是宿主感染所必需的。

Inv1: an Edwardsiella tarda invasin and a protective immunogen that is required for host infection.

机构信息

Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, China.

出版信息

Fish Shellfish Immunol. 2012 Apr;32(4):586-92. doi: 10.1016/j.fsi.2012.01.016. Epub 2012 Jan 21.

DOI:10.1016/j.fsi.2012.01.016
PMID:22289712
Abstract

Invasin is an outer membrane protein that is known to mediate entry of enteric bacteria into mammalian cells. In this study, we analyzed the function and immunoprotective potential of the invasin Inv1 from Edwardsiella tarda, a serious fish pathogen that can also infect humans. In silico analysis indicated that Inv1 possesses a conserved N-terminal DUF3442 domain and a C-terminal group 1 bacterial Ig-like domain. Subcellular localization analysis showed that Inv1 is exposed on cell surface and could be recognized by specific antibodies. Mutation of inv1 had no effect on bacterial growth but attenuates overall bacterial virulence and impaired the ability of E. tarda to attach and invade into host cells. Consistent with these observations, antibody blocking of Inv1 inhibited E. tarda infection of host cells. To examine the immunoprotective potential of Inv1, recombinant Inv1 (rInv1) corresponding to the DUF3442 domain was purified and used to vaccinate Japanese flounder (Paralichthys olivaceus). The results showed that rInv1 induced strong protection against lethal-dose challenge of E. tarda. ELISA analysis showed that rInv1-vaccinated fish produced specific serum antibodies that could enhance the serum bactericidal activity against E. tarda. Taken together, these results indicate that Inv1 is a surface-localized virulence factor that is involved in host infection and can induce effective immunoprotection when used as a subunit vaccine.

摘要

入侵素是一种外膜蛋白,已知能介导肠道细菌进入哺乳动物细胞。在这项研究中,我们分析了爱德华氏菌的入侵素 Inv1 的功能和免疫保护潜力,爱德华氏菌是一种严重的鱼类病原体,也能感染人类。计算机分析表明,Inv1 具有保守的 N 端 DUF3442 结构域和 C 端组 1 细菌 Ig 样结构域。亚细胞定位分析表明,Inv1 暴露在细胞表面,可以被特异性抗体识别。inv1 的突变对细菌生长没有影响,但削弱了细菌的整体毒力,并损害了 E. tarda 附着和侵入宿主细胞的能力。与这些观察结果一致,抗体阻断 Inv1 抑制了 E. tarda 感染宿主细胞。为了研究 Inv1 的免疫保护潜力,我们纯化了与 DUF3442 结构域相对应的重组 Inv1(rInv1),并用于接种日本牙鲆(Paralichthys olivaceus)。结果表明,rInv1 能强烈抵抗致死剂量的 E. tarda 攻毒。ELISA 分析表明,rInv1 疫苗接种的鱼产生了特异性的血清抗体,可以增强血清对 E. tarda 的杀菌活性。综上所述,这些结果表明,Inv1 是一种表面定位的毒力因子,参与宿主感染,并可作为亚单位疫苗诱导有效的免疫保护。

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