论文题目：Interkingdom sensing of fungal tyrosol promotes bacterial antifungal T6SS activity in the murine gut
论文作者：Lingfang Zhu#, Yuxin Zuo#, Rui Cui#, Peishuai Fu, Yuqi Liu, Zhuo Wang, Xinquan He, Danyang Yu, Zhiyan Wei, Shuyu Li, Yang Wang, Changfu Li, Yao Wang, DeFeng Li*, ShuangJiang Liu*, Xihui Shen*
论文摘要：Type VI secretion systems (T6SSs) are molecular machines used by bacteria to release effectors that target either host cells, competing bacteria or fungi. Regulatory mechanisms underlying antifungal T6SS activity remain unexplored. Here we show, using mouse infection with wild-type and T6SS mutant bacteria, that T6SS activity of the enteropathogen, Yersinia pseudotuberculosis (Yptb), reduces fungal prevalence in the gut microbiota and has direct activity on Candida albicans. Screening of bacterial effector mutant strains, and structural and biochemical analyses identify TfeC as an antifungal chitinase T6SS effector that can kill C. albicans. In vivo experiments confirm that TfeC expression promotes Yptb colonization and reduces C. albicans abundance. We also show that Yptb senses the fungal quorum-sensing molecule, tyrosol, through the two-component system, EnvZ–OmpR, and responds by activating T6SS4. Our findings suggest that Yptb modulates its antifungal activities by detecting changes in fungal population density cues, revealing a mechanism of fungal-bacterial interkingdom communication mediated by fungal quorum-sensing molecules.
VI型分泌系统（T6SS）是细菌分泌效应蛋白的分子机器，可靶向宿主细胞、竞争性细菌或真菌，但其抗真菌活性的调控机制尚未明确。本研究通过假结核耶尔森菌（Yersinia pseudotuberculosis，Yptb）野生型及T6SS突变菌株感染小鼠实验发现，Yptb可以通过T6SS降低肠道菌群中真菌的占比，且对白色念珠菌具有直接抑制作用。通过筛选细菌效应蛋白突变株，并结合结构与生化分析，我们鉴定出TfeC是一类具有抗真菌活性的几丁质酶类T6SS效应蛋白，可直接杀灭白色念珠菌。通过细菌在小鼠体内的定植和杀真菌实验发现，Yptb通过分泌TfeC可增强自身在肠道内的定植，同时发挥体内杀白色念珠菌功能。进一步研究发现，Yptb可以通过EnvZ-OmpR双组分系统感知真菌群体感应分子酪醇，进而激活抗真菌系统T6SS4/TfeC。上述结果表明，Yptb能够通过识别真菌群体密度信号的变化调控自身抗真菌活性，揭示了真菌群体感应分子介导的真菌与细菌间的跨界通讯机制。
原文链接：https://doi.org/10.1038/s41564-025-02208-z