CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, People's Republic of China.
University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
Environ Microbiol. 2018 Mar;20(3):1224-1239. doi: 10.1111/1462-2920.14068. Epub 2018 Mar 25.
Toxin/antitoxin (TA) loci are commonly found in mobile genetic elements such as plasmids and prophages. However, the physiological functions of these TA loci in prophages and cross-regulation among these TA loci remain largely unexplored. Here, we characterized a newly discovered type II TA pair, ParE /CopA , in the CP4So prophage in Shewanella oneidensis. We demonstrated that ParE /CopA plays a critical role in the maintenance of CP4So in host cells after its excision. The toxin ParE inhibited cell growth, resulting in filamentous growth and eventually cell death. The antitoxin CopA neutralized the toxicity of ParE through direct protein-protein interactions and repressed transcription of the TA operon by binding to a DNA motif in the promoter region containing two inverted repeats [5'-GTANTAC (N) GTANTAC-3']. CopA also repressed transcription of another TA system PemK /PemI in megaplasmid pMR-1 of S. oneidensis through binding to a highly similar DNA motif in its promoter region. CopA homologs are widely spread in Shewanella and other Proteobacteria, either as a component of a TA pair or as orphan antitoxins. Our study thus illustrated the cross-regulation of the TA systems in different mobile genetic elements and expanded our understanding of the physiological function of TA systems.
毒素/抗毒素 (TA) 基因座通常存在于移动遗传元件中，如质粒和前噬菌体。然而，这些 TA 基因座在前噬菌体中的生理功能以及它们之间的交叉调控在很大程度上仍未得到探索。在这里，我们描述了希瓦氏菌属 CP4So 前噬菌体中一种新发现的 II 型 TA 对 ParE/CopA。我们证明 ParE/CopA 在 CP4So 从前宿主细胞中切除后对其在宿主细胞中的维持起着至关重要的作用。毒素 ParE 抑制细胞生长，导致丝状生长，最终导致细胞死亡。抗毒素 CopA 通过直接蛋白-蛋白相互作用中和 ParE 的毒性，并通过结合包含两个反向重复 [5'-GTANTAC (N) GTANTAC-3'] 的启动子区域中的 DNA 模体来抑制 TA 操纵子的转录。CopA 还通过结合其启动子区域中高度相似的 DNA 模体来抑制希瓦氏菌属 megaplasmid pMR-1 中的另一个 TA 系统 PemK/PemI 的转录。CopA 同源物广泛存在于希瓦氏菌属和其他变形菌门中，要么作为 TA 对的一个组成部分，要么作为孤儿抗毒素。因此，我们的研究说明了不同移动遗传元件中 TA 系统的交叉调控，并扩展了我们对 TA 系统生理功能的理解。
