Inhibition of phage infection by secondary metabolites produced by actinobacterial species

放线菌产生的次级代谢产物抑制噬菌体感染

• 批准号: 464434020
• 负责人: Professorin Dr. Julia Frunzke
• 金额: --
• 依托单位: AG Systemische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/464434020?language=en
• 关键词: Inhibition; phage; infection; secondary; metabolites

Members of the actinobacterial genus Streptomyces are prolific producers of natural products with a wide range of biological activities. This repertoire of bioactive molecules has been harnessed for medical and agricultural purposes, as for example ⅔ of known antibiotics of microbial origin are produced by Streptomyces. However, a potential role in defense against viral infection has only been recognized recently. How phage infection actually alters the antibiotic profile of the host and how this reaction may add to the protection against viral predation at the multicellular level has not been addressed yet. In preliminary experiments, we have isolated and characterized more than 15 novel phages infecting different Streptomyces strains. Interestingly, we observed intensive production of secondary metabolites at the infection zone in plaques formed by Streptomyces coelicolor phages. Furthermore, preliminary data revealed that different aminoglycoside antibiotics efficiently protect Streptomyces species from phage predation. The proposed project will focus on two main objectives. Objective I will address the impact of phage infection on the antibiotic profiles of Streptomyces strains and their potential role in chemical defense strategies. Objective II will specifically investigate the antiviral ‘mode of action’ of aminoglycoside antibiotics. Overall, there is a high potential for synergy between WPs of the different objectives as well as with further projects within the SPP. Experiments will cover intensive screenings as well as molecular/mechanistic approaches addressing the question which stage in phage infection is affected by the particular molecules.Overall, experiments planned in the proposed project will provide important insights into the chemical defense of Streptomyces to phage infection and have the potential to discover new concepts in antiviral defense at the multicellular level.

放线菌属链霉菌属的成员是具有广泛生物活性的天然产物的多产生产者。这些生物活性分子已被用于医疗和农业目的，例如 2/3 的已知微生物来源抗生素是由链霉菌产生的。然而，最近才认识到其在防御病毒感染方面的潜在作用。噬菌体感染实际上如何改变宿主的抗生素特征，以及这种反应如何在多细胞水平上增强对病毒捕食的保护，尚未得到解决。在初步实验中，我们分离并鉴定了超过 15 种感染不同链霉菌菌株的新型噬菌体。有趣的是，我们观察到在天蓝色链霉菌噬菌体形成的斑块的感染区域大量产生次级代谢产物。此外，初步数据显示，不同的氨基糖苷类抗生素可有效保护链霉菌免受噬菌体捕食。 拟议项目将侧重于两个主要目标。目标我将讨论噬菌体感染对链霉菌菌株抗生素谱的影响及其在化学防御策略中的潜在作用。目标 II 将专门研究氨基糖苷类抗生素的抗病毒“作用方式”。总体而言，不同目标的工作组之间以及与 SPP 内的进一步项目之间存在很大的协同潜力。实验将涵盖密集筛选以及分子/机械方法，解决噬菌体感染的哪个阶段受特定分子影响的问题。总体而言，拟议项目中计划的实验将为链霉菌对噬菌体感染的化学防御提供重要见解，并有可能发现多细胞水平抗病毒防御的新概念。