Hachani Abderrahman, Allsopp Luke P, Oduko Yewande, Filloux Alain
From the MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
From the MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom
J Biol Chem. 2014 Jun 20;289(25):17872-84. doi: 10.1074/jbc.M114.563429. Epub 2014 May 2.
The bacterial type VI secretion system (T6SS) is a supra-molecular complex akin to bacteriophage tails, with VgrG proteins acting as a puncturing device. The Pseudomonas aeruginosa H1-T6SS has been extensively characterized. It is involved in bacterial killing and in the delivery of three toxins, Tse1-3. Here, we demonstrate the independent contribution of the three H1-T6SS co-regulated vgrG genes, vgrG1abc, to bacterial killing. A putative toxin is encoded in the vicinity of each vgrG gene, supporting the concept of specific VgrG/toxin couples. In this respect, VgrG1c is involved in the delivery of an Rhs protein, RhsP1. The RhsP1 C terminus carries a toxic activity, from which the producing bacterium is protected by a cognate immunity. Similarly, VgrG1a-dependent toxicity is associated with the PA0093 gene encoding a two-domain protein with a putative toxin domain (Toxin_61) at the C terminus. Finally, VgrG1b-dependent killing is detectable upon complementation of a triple vgrG1abc mutant. The VgrG1b-dependent killing is mediated by PA0099, which presents the characteristics of the superfamily nuclease 2 toxin members. Overall, these data develop the concept that VgrGs are indispensable components for the specific delivery of effectors. Several additional vgrG genes are encoded on the P. aeruginosa genome and are not linked genetically to other T6SS genes. A closer inspection of these clusters reveals that they also encode putative toxins. Overall, these associations further support the notion of an original form of secretion system, in which VgrG acts as the carrier.
细菌VI型分泌系统（T6SS）是一种类似于噬菌体尾部的超分子复合物，VgrG蛋白充当穿刺装置。铜绿假单胞菌H1-T6SS已得到广泛表征。它参与细菌杀伤以及三种毒素Tse1-3的递送。在此，我们证明了H1-T6SS共调控的三个vgrG基因vgrG1abc对细菌杀伤的独立贡献。每个vgrG基因附近都编码一种推定毒素，这支持了特定VgrG/毒素配对的概念。在这方面，VgrG1c参与一种Rhs蛋白RhsP1的递送。RhsP1的C末端具有毒性活性，产生该蛋白的细菌通过同源免疫得到保护。同样，VgrG1a依赖性毒性与PA0093基因相关，该基因编码一种双结构域蛋白，其C末端具有推定毒素结构域（毒素_61）。最后，在三重vgrG1abc突变体互补后可检测到VgrG1b依赖性杀伤作用。VgrG1b依赖性杀伤作用由PA0099介导，PA0099具有超家族核酸酶2毒素成员的特征。总体而言，这些数据进一步完善了VgrG是效应物特异性递送不可或缺的组成部分这一概念。铜绿假单胞菌基因组上还编码了几个额外的vgrG基因，它们在遗传上与其他T6SS基因没有联系。对这些基因簇的进一步研究表明，它们也编码推定毒素。总体而言，这些关联进一步支持了一种原始分泌系统形式的概念，其中VgrG充当载体。
