State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
School of Medicine, Southern University of Science and Technology, Shenzhen, China.
ISME J. 2022 Jul;16(7):1765-1775. doi: 10.1038/s41396-022-01228-5. Epub 2022 Mar 30.
Vibrio cholerae, the etiological pathogen of cholera, employs its type VI secretion system (T6SS) as an effective weapon to survive in highly competitive communities. Antibacterial and anti-eukaryotic functions of the T6SS depend on its secreted effectors that target multiple cellular processes. However, the mechanisms that account for effector diversity and different effectiveness during interspecies competition remain elusive. Here we report that environmental cations and temperature play a key role in dictating cellular response and effector effectiveness during interspecies competition mediated by the T6SS of V. cholerae. We found that V. cholerae could employ its cell-wall-targeting effector TseH to outcompete the otherwise resistant Escherichia coli and the V. cholerae immunity deletion mutant ∆tsiH when Mg or Ca was supplemented. Transcriptome and genetic analyses demonstrate that the metal-sensing PhoPQ two-component system is important for Mg-dependent sensitivity. Competition analysis in infant mice shows that TseH was active under in vivo conditions. Using a panel of V. cholerae single-effector active mutants, we further show that E. coli also exhibited variable susceptibilities to other T6SS effectors depending on cations and temperatures, respectively. Lastly, V. cholerae effector VasX could sensitize Pseudomonas aeruginosa to its intrinsically resistant antibiotic irgasan in a temperature-dependent manner. Collectively, these findings suggest that abiotic factors, that V. cholerae frequently encounters in natural and host environments, could modulate cellular responses and dictate the competitive fitness conferred by the T6SS effectors in complex multispecies communities.
霍乱弧菌是霍乱的病原体，它利用其类型 VI 分泌系统（T6SS）作为一种有效的武器，在竞争激烈的环境中生存。T6SS 的抗菌和抗真核生物功能依赖于其分泌的效应物，这些效应物针对多种细胞过程。然而，导致效应物多样性和种间竞争中不同效果的机制仍然难以捉摸。在这里，我们报告环境阳离子和温度在决定种间竞争中介导的 T6SS 的细胞反应和效应物有效性方面起着关键作用。我们发现，当补充 Mg 或 Ca 时，霍乱弧菌可以利用其针对细胞壁的效应物 TseH 来竞争原本具有抗性的大肠杆菌和霍乱弧菌免疫缺失突变体 ∆tsiH。转录组和遗传分析表明，金属感应 PhoPQ 双组分系统对于 Mg 依赖性敏感性很重要。在婴儿小鼠中的竞争分析表明，TseH 在体内条件下是活跃的。使用一组霍乱弧菌单效应物活性突变体，我们进一步表明，大肠杆菌也根据阳离子和温度分别对其他 T6SS 效应物表现出不同的敏感性。最后，霍乱弧菌效应物 VasX 可以以温度依赖的方式使铜绿假单胞菌对其固有抗性抗生素 irgasan 敏感。总的来说，这些发现表明，霍乱弧菌在自然和宿主环境中经常遇到的非生物因素可以调节细胞反应，并决定 T6SS 效应物在复杂多物种群落中赋予的竞争适应性。
