The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems
The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems
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与多种延伸毒素结构域融合的 Hcp 蛋白代表了 VI 型分泌系统中抗菌效应子的新模式。
DOI：
10.1080/21505594.2017.1279374
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发表时间：
2017-01-01
期刊：
影响因子：
5.2
通讯作者：
Yao, Huochun
中科院分区：
文献类型：
--
作者：
Ma, Jiale;Pan, Zihao;Yao, Huochun
VI 型分泌系统（T6SS）是一种广泛的分子武器，被许多细菌物种用来瞄准真核宿主细胞或竞争细菌。使用动态注射机制，T6SS 可以将多种效应物直接递送到受体细胞中。在这里，我们报告了一个新的 T6SS 效应子家族，由携带不同毒素结构域的扩展 Hcp 编码。生物信息学分析表明，这些带有C末端延伸毒素的Hcp，称为Hcp-ET，广泛存在于肠杆菌科细菌中。为了验证我们的发现，测试了 Hcp-ET1 的抗菌作用，并通过 T6SS 依赖性递送预测的 HNH-DNase 活性有效抑制靶细胞生长。进一步的研究表明，Hcp-ET2 通过 Tle1 磷脂酶（由 DUF2235 结构域编码）活性介导细菌间拮抗作用。值得注意的是，对蛋白质同源性和基因组邻域的综合分析表明，Hcp-ET3-4 在 C 端与 2 个毒素结构域（Pyocin S3 和 Colicin-DNase）融合，其编码基因后面有 3 个同源免疫基因的重复。然而，一些细菌编码分离的 hcp-et3 和孤儿 et4 (et4(O1)) 基因，这是由 Pyocin S3 和 Colicin-DNase 编码片段之间的融合区域中的终止密码子突变引起的。我们的结果表明，这两种毒素都具有抗菌作用。此外，同源免疫蛋白的所有重复都有助于中和 Pyocin S3 和 Colicin 的 DNase 毒性，这在之前尚未有报道。总之，我们提出Hcp-ET蛋白是多态性T6SS效应子，从而呈现出一种新的T6SS效应子编码模式。
The type VI secretion system (T6SS) is a widespread molecular weapon deployed by many bacterial species to target eukaryotic host cells or rival bacteria. Using a dynamic injection mechanism, diverse effectors can be delivered by T6SS directly into recipient cells. Here, we report a new family of T6SS effectors encoded by extended Hcps carrying diverse toxin domains. Bioinformatic analyses revealed that these Hcps with C-terminal extension toxins, designated as Hcp-ET, exist widely in the Enterobacteriaceae. To verify our findings, Hcp-ET1 was tested for its antibacterial effect, and showed effective inhibition of target cell growth via the predicted HNH-DNase activity by T6SS-dependent delivery. Further studies showed that Hcp-ET2 mediated interbacterial antagonism via a Tle1 phospholipase (encoded by DUF2235 domain) activity. Notably, comprehensive analyses of protein homology and genomic neighborhoods revealed that Hcp-ET3-4 is fused with 2 toxin domains (Pyocin S3 and Colicin-DNase) C-terminally, and its encoding gene is followed 3 duplications of the cognate immunity genes. However, some bacteria encode a separated hcp-et3 and an orphan et4 (et4(O1)) genes caused by a termination-codon mutation in the fusion region between Pyocin S3 and Colicin-DNase encoding fragments. Our results demonstrated that both of these toxins had antibacterial effects. Further, all duplications of the cognate immunity protein contributed to neutralize the DNase toxicity of Pyocin S3 and Colicin, which has not been reported previously. In conclusion, we propose that Hcp-ET proteins are polymorphic T6SS effectors, and thus present a novel encoding pattern of T6SS effectors.