华盛顿大学Joseph D. Mougous课题组的最新研究揭示了伞形毒素的独特结构使其能够采用两级分子风险对冲策略，实现细菌间的拮抗作用。这一研究成果发表在2025年12月2日出版的国际学术期刊《细胞》上。
课题组研究人员表明，伞状颗粒的精致特异性源于凝集素介导的物种特异性结合，先前未描述的高变表面糖缀合物。一种这样的凝集素及其寡糖底物的低温电镜（cryo-EM）结构通过协调识别多个聚糖特征来定义靶向的分子基础。几种目标物种的生化和遗传研究，结合凝集素交换实验，支持一种模型，即在凝集素组成和毒素多态性水平上的S. colelicolor伞毒素多样化代表了一种独特的两层下注对冲策略。生物信息学分析支持这一观点，认为伞状毒素的非共同结构为链霉菌提供了一种通用策略，以对抗一系列不可预测的竞争对手。
据了解，细菌存在于竞争激烈和快速变化的环境中，在这种环境中，未来威胁的性质无法轻易预测。彩色链霉菌产生三种抗菌保护伞颗粒，其中含有不同的多态毒素结构域和重叠的六种不同的凝集素。
附：英文原文
Title: The unique architecture of umbrella toxins permits a two-tiered molecular bet-hedging strategy for interbacterial antagonism
Author: Qinqin Zhao, Jiri Vlach, Young-Jun Park, Yongjun Tan, Savannah K. Bertolli, Pooja Srinivas, Pinyu Liao, Connor R. Fitzpatrick, Jeffery L. Dangl, Parastoo Azadi, Frank DiMaio, S. Brook Peterson, Dapeng Zhang, David Veesler, Joseph D. Mougous
Issue&Volume: 2025-12-02
Abstract: Bacteria exist in competitive and rapidly changing environments in which the nature of future threats cannot be easily predicted. Streptomyces coelicolor produces three antibacterial umbrella particles that harbor distinct polymorphic toxin domains and an overlapping set of six diversified lectins. Here, we show that the exquisite specificity of umbrella particles derives from lectin-mediated species-specific binding to previously undescribed hypervariable surface glycoconjugates. A cryo-electron microscopy (cryo-EM) structure of one such lectin in complex with its oligosaccharide substrate defines the molecular basis for targeting through the coordinated recognition of multiple glycan features. Biochemical and genetic studies of several target species, in conjunction with lectin-swapping experiments, support a model whereby S. coelicolor umbrella toxin diversification at the levels of lectin composition and toxin polymorphism represents a unique, two-tiered bet-hedging strategy. Bioinformatic analyses support this as a means by which the unusual architecture of umbrella toxins offers Streptomyces a generalizable strategy to antagonize an unpredictable array of competitors.
DOI: 10.1016/j.cell.2025.10.044
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01249-8