Understanding the nature of anti-phage defense islands in microbes

了解微生物中抗噬菌体防御岛的性质

• 批准号: 464312965
• 负责人: Professor Dr. Rotem Sorek, Ph.D.
• 金额: --
• 依托单位: Department of Molecular Genetics
• 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/464312965?language=en
• 关键词: Understanding; nature; anti; phage; defense

Bacteria are engaged in a continuous arms race in which they seek to defend themselves against rapidly evolving phages. To this end, bacteria evolved dedicated defense systems, including restriction-modification, CRISPR-Cas, abortive infection, and a large diversity of additional defense systems. Analysis of bacterial and archaeal genomes have shown that defense systems are non-randomly distributed in microbial genomes, and are clustered to specific genomic locations that were termed “defense islands”. This property of defense systems allowed the prediction, and later the experimental verification, of numerous novel anti-phage defense systems based on their preferential genomic localization near restriction systems, CRISPR-Cas, and other known defense systems in multiple microbial genomes. Although the concept of defense islands have been instrumental for the recent discovery of many defense systems, the nature of defense islands themselves remained vague. What are defense islands? What defines a defense island? Are defense islands involved in transferring defense systems between microbial genomes? If so, how? How often do they appear in microbial genomes? These questions are currently completely unanswered and will be addressed in the current proposed project. As part of our preliminary, unpublished results, we developed methodologies that allow to identify the exact boundaries of defense islands within the microbial genome. With these data, we found preliminary evidence suggesting that some defense islands are mobile genetic elements dedicated for carrying and mobilizing defense systems between genomes. In the current proposal we present a combined computational/experimental plan to comprehensively map defense islands in a large set of microbial genomes, understand their content, integration patterns, and mobility between genomes. This will allow us to understand how defense islands spread phage resistance traits between genomes, and furthermore to discover new families of anti-phage defense systems that so far escaped detection.

细菌正在进行一场持续的军备竞赛，在这场竞赛中，它们试图保护自己免受快速进化的噬菌体的攻击。为此，细菌进化出了专门的防御系统，包括限制性内切酶修饰、CRISPR-CA、流产感染和大量多样性的额外防御系统。对细菌和古菌基因组的分析表明，防御系统在微生物基因组中是非随机分布的，并聚集在特定的基因组位置，这些位置被称为“防御岛”。防御系统的这一特性使得许多新型的抗噬菌体防御系统得以预测，并在后来的实验中得到验证，这些系统基于限制性内切酶系统、CRISPR-CAS和其他已知的多个微生物基因组中的防御系统。尽管防御岛的概念对最近许多防御系统的发现起到了重要作用，但防御岛本身的性质仍然很模糊。什么是防御岛？防御岛的定义是什么？防御岛是否参与了微生物基因组间防御系统的转移？如果是这样的话，是如何做到的呢？它们多长时间出现在微生物基因组中？这些问题目前完全没有得到回答，将在目前的拟议项目中予以解决。作为我们初步的、未发表的结果的一部分，我们开发了允许识别微生物基因组中防御岛的准确边界的方法。通过这些数据，我们发现了初步证据表明，一些防御岛是可移动的遗传元件，专门用于携带和动员基因组之间的防御系统。在当前的提案中，我们提出了一个计算/实验相结合的计划，以全面绘制大量微生物基因组中的防御岛，了解它们的内容、整合模式和基因组之间的移动性。这将使我们了解防御岛如何在基因组之间传播噬菌体抗性特征，并进一步发现迄今未被发现的抗噬菌体防御系统的新家族。