ACS Chem Biol. 2021 Mar 19;16(3):501-509. doi: 10.1021/acschembio.0c00901. Epub 2021 Feb 17.
Cell-to-cell communication via chemical signals is an essential mechanism that pathogenic bacteria use to coordinate group behaviors and promote virulence. The () gene cluster is distributed in more than 500 strains of proteobacteria including both plant and human pathogens. The cluster has been implicated in the production of signaling molecules important for virulence; however, the regulatory impact of these signaling molecules on virulence had not been elucidated. Using the insect pathogen L48 as a model, we demonstrated that -encoded biosynthetic enzymes produce PVF autoinducers that regulate the expression of genes and a gene encoding the toxin monalysin via quorum sensing. In addition, PVF autoinducers regulate the expression of nearly 200 secreted and membrane proteins, including toxins, motility proteins, and components of the type VI secretion system, which play key roles in bacterial virulence, colonization, and competition with other microbes. Deletion of also altered the secondary metabolome. Six major compounds upregulated by PVF autoinducers were isolated and structurally characterized, including three insecticidal 3-indolyl oxazoles, the labradorins, and three antimicrobial pyrrolizidine alkaloids, the pyreudiones. The signaling properties of PVF autoinducers and their wide-ranging regulatory effects indicate multifaceted roles of PVF in controlling cell physiology and promoting virulence. The broad genome distribution of suggests that PVF-mediated signaling is relevant to many bacteria of agricultural and biomedical significance.
通过化学信号进行细胞间通讯是一种重要的机制，病原细菌利用这种机制来协调群体行为并促进毒力。（）基因簇分布在包括植物和人类病原体在内的 500 多种变形菌中。该簇与产生对毒力很重要的信号分子有关；然而，这些信号分子对毒力的调节作用尚未阐明。我们使用昆虫病原体 L48 作为模型，证明了 -编码的生物合成酶产生 PVF 自动诱导物，通过群体感应调节 基因和编码毒素 monalysin 的基因的表达。此外，PVF 自动诱导物调节近 200 种分泌和膜蛋白的表达，包括毒素、运动蛋白和 VI 型分泌系统的组成部分，这些蛋白在细菌毒力、定植和与其他微生物竞争中发挥关键作用。缺失 也改变了次级代谢组。通过 PVF 自动诱导物上调的六种主要化合物被分离并进行了结构表征，包括三种杀虫 3-吲哚基恶唑、labradorins 和三种抗菌吡咯里西啶生物碱、pyreudiones。PVF 自动诱导物的信号特性及其广泛的调节作用表明，PVF 在控制细胞生理和促进毒力方面具有多方面的作用。的广泛基因组分布表明，PVF 介导的信号与许多具有农业和医学意义的细菌有关。
