MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Section of Structural Biology, Department of Medicine, Imperial College London, London SW7 2AZ, UK.
Cell Rep. 2019 Oct 1;29(1):187-201.e7. doi: 10.1016/j.celrep.2019.08.094.
The type VI secretion system (T6SS) is crucial in interbacterial competition and is a virulence determinant of many Gram-negative bacteria. Several T6SS effectors are covalently fused to secreted T6SS structural components such as the VgrG spike for delivery into target cells. In Pseudomonas aeruginosa, the VgrG2b effector was previously proposed to mediate bacterial internalization into eukaryotic cells. In this work, we find that the VgrG2b C-terminal domain (VgrG2b) elicits toxicity in the bacterial periplasm, counteracted by a cognate immunity protein. We resolve the structure of VgrG2b and confirm it is a member of the zinc-metallopeptidase family of enzymes. We show that this effector causes membrane blebbing at midcell, which suggests a distinct type of T6SS-mediated growth inhibition through interference with cell division, mimicking the impact of β-lactam antibiotics. Our study introduces a further effector family to the T6SS arsenal and demonstrates that VgrG2b can target both prokaryotic and eukaryotic cells.
VI 型分泌系统（T6SS）在细菌间竞争中至关重要，是许多革兰氏阴性菌的毒力决定因素。几种 T6SS 效应子与分泌的 T6SS 结构成分（如 VgrG 刺突）共价融合，以便将其递送至靶细胞。在铜绿假单胞菌中，先前提出 VgrG2b 效应子介导细菌内化进入真核细胞。在这项工作中，我们发现 VgrG2b 的 C 端结构域（VgrG2b）在细菌周质中引发毒性，被同源免疫蛋白拮抗。我们解析了 VgrG2b 的结构，并证实它是锌金属蛋白酶家族的酶的成员。我们表明，这种效应子在中膜引起膜泡形成，这表明通过干扰细胞分裂，以一种独特的方式抑制 T6SS 介导的生长，类似于β-内酰胺类抗生素的影响。我们的研究为 T6SS 武器库引入了另一个效应子家族，并表明 VgrG2b 可以靶向原核和真核细胞。
