Liu Ya, Zhang Zheng, Wang Feng, Li Dan-Dan, Li Yue-Zhong
State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China.
Suzhou Research Institute, Shandong University, Suzhou 215123, China.
Comput Struct Biotechnol J. 2020 Nov 23;18:3723-3733. doi: 10.1016/j.csbj.2020.11.003. eCollection 2020.
Toxic effectors secreted by the type VI secretion system (T6SS) facilitate interbacterial warfare, as well as pathogenesis toward humans, animals and plants. However, systematically predicting T6SS effectors remains challenging due to their sequence and functional diversity. In this study, we systematically identified putative T6SS toxic effectors in prokaryotic genomes on the basis of the observation that genes encoding adaptor proteins and genes encoding cognate effector proteins are generally adjacent in the genome. Adaptor proteins are mediators that help to load their cognate effectors onto the T6SS spike complex. The contextual genes of the known adaptor proteins (DUF1795, DUF2169 or DUF4123) all exhibited a high proportion of encoding T6SS spike complex protein (VgrG or PAAR) and effector proteins. On the basis of the genomic context, we found that PRK06147 might be a novel adaptor protein. These four adaptors are widely distributed among the bacterial genomes. From neighbors of 5297 adaptor genes, we identified 1356 putative effector genes from 92 different families, and two-thirds were currently annotated as hypothetical proteins or as having unknown functions. Our results indicate that each class of adaptors can be used as an effective marker to identify T6SS toxic effectors, moreover, this approach can promote the discovery of new effectors.
VI型分泌系统（T6SS）分泌的毒性效应蛋白有助于细菌间的竞争，以及对人类、动物和植物的致病作用。然而，由于T6SS效应蛋白的序列和功能具有多样性，系统地预测它们仍然具有挑战性。在本研究中，基于编码衔接蛋白的基因和编码同源效应蛋白的基因在基因组中通常相邻这一观察结果，我们系统地鉴定了原核生物基因组中假定的T6SS毒性效应蛋白。衔接蛋白是有助于将其同源效应蛋白加载到T6SS刺突复合体上的介质。已知衔接蛋白（DUF1795、DUF2169或DUF4123）的上下文基因都显示出高比例的编码T6SS刺突复合体蛋白（VgrG或PAAR）和效应蛋白。基于基因组上下文，我们发现PRK06147可能是一种新型衔接蛋白。这四种衔接蛋白广泛分布于细菌基因组中。从5297个衔接蛋白基因的邻近基因中，我们从92个不同家族中鉴定出1356个假定的效应蛋白基因，其中三分之二目前被注释为假定蛋白或功能未知。我们的结果表明，每一类衔接蛋白都可以用作鉴定T6SS毒性效应蛋白的有效标记，此外，这种方法可以促进新效应蛋白的发现。
