沈锡辉、韦革宏等《ISME Journal》2024年

论文题目：Trojan horse like T6SS effector TepC mediates both interference competition and exploitative competition

论文作者：Li Song^#, Lei Xu^#, Tong Wu^#, Zhenkun Shi, Hafiz Abdul Kareem, Zhuo Wang, Qingyun Dai, Chenghao Guo, Junfeng Pan, Mingming Yang, Xiaomeng Wei, Yao Wang, Gehong Wei^*, Xihui Shen^*

论文摘要：The type VI secretion system (T6SS) is a bacterial weapon capable of delivering antibacterial effectors to kill competing cells for interference competition, as well as secreting metal ion scavenging effectors to acquire essential micronutrients for exploitation competition. However, no T6SS effectors that can mediate both interference competition and exploitation competition have been reported. In this study, we identified a unique T6SS-1 effector in  Yersinia pseudotuberculosis  named TepC, which plays versatile roles in microbial communities. First, secreted TepC acts as a proteinaceous siderophore that binds to iron and mediates exploitative competition. Additionally, we discovered that TepC has DNase activity, which gives it both contact-dependent and contact-independent interference competition abilities. In conditions where iron is limited, the iron-loaded TepC is taken up by target cells expressing the outer membrane receptor TdsR. For kin cells encoding the cognate immunity protein TipC, TepC facilitates iron acquisition, and its toxic effects are neutralized. On the other hand, nonkin cells lacking TipC are enticed to uptake TepC and are killed by its DNase activity. Therefore, we have uncovered a T6SS effector, TepC, that functions like a "Trojan horse" by binding to iron ions to provide a valuable resource to kin cells, whereas punishing cheaters that do not produce public goods. This lure-to-kill mechanism, mediated by a bifunctional T6SS effector, may offer new insights into the molecular mechanisms that maintain stability in microbial communities.

细菌VI型分泌系统（T6SS）是一种细菌武器，通过分泌抗菌效应蛋白实施干扰竞争以杀死竞争细胞，或分泌螯合金属离子的效应蛋白以发挥营养剥削竞争。然而，目前尚未发现可以同时介导两种竞争的T6SS效应蛋白。在这项研究中，我们在假结核耶尔森氏菌中发现了一种独特的 T6SS-1 效应蛋白TepC，它在微生物群落中发挥着多重作用。首先，TepC 作为蛋白质类铁载体，与铁结合并介导剥削性竞争。此外，TepC 具有 DNase 活性，可以同时介导接触依赖型和接触非依赖型杀菌竞争。在铁限制条件下，螯合铁的 TepC 能够被表达外膜受体 TdsR 的靶细胞所摄取。TepC帮助对于编码同源免疫蛋白 TipC 的亲属细胞获取铁。然而缺乏 TipC 的非亲缘细胞尽管摄取了TepC，却被其 DNase 活性杀死。综上，我们发现了一种“特洛伊木马”式的T6SS效应蛋白TepC，它能够通过与铁离子结合为亲属细胞提供宝贵的资源，同时可以惩罚不生产公共物品的作弊者。这种由双功能 T6SS 效应蛋白所介导的诱杀机制可能为维持微生物群落稳定性提供新的见解。

文章链接：https://doi.org/10.1093/ismejo/wrad028