Discovery and characterization of peptides that direct communication in phages and bacteria

指导噬菌体和细菌通讯的肽的发现和表征

• 批准号: 379070190
• 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/379070190?language=en
• 关键词: Discovery; characterization; peptides; direct; communication

In every infection, temperate phages need to decide whether to replicate and lyse their host or to lysogenize and keep the host viable. As part of the first term of the current SPP2002 Priority Programme, we discovered that phages infecting Bacillus bacteria use a small-molecule communication system to coordinate lysis-lysogeny decisions (Erez et al., Nature 2017; Stokar-Avihail et al, Cell Host & Microbe 2019). During infection of its host cell, the phage produces a short (6aa-10aa) communication peptide that is produced by a µ-protein and released to the medium. In subsequent infections, progeny phages measure the concentration of this peptide and lysogenize if the concentration is sufficiently high. We termed this system the “arbitrium” system (“decision” in Latin). Our results showed that many phages harbor arbitrium-encoding µ-proteins and use them in order to communicate and coordinate infection decisions. However, so far all arbitrium homologs were found in prophages residing in bacterial genomes belonging to the taxonomic family Bacillaceae, and it is currently unknown whether phages infecting bacteria of other taxonomic groups also utilize peptide-based communication strategies for lysis/lysogeny decisions. In the current project we will attempt to discover additional, arbitrium-like systems in phages infecting non-bacillus species. As the discovery of the arbitrium system forms the first demonstration of actual communication between viruses, it represents a new paradigm in virology that may extend beyond the prokaryotic world. Understanding the diversity and constraints of phage communication systems will not only help us to assign function to hundreds of µ-proteins in bacterial and phage genomes, but may also set the stage for future such discoveries in viruses that infect higher organisms.As part of the first 3 years of SPP2002 we developed a general platform for the computational discovery and experimental validation of µ-proteins-based communication systems across thousands of genomes of interest. We showed that this platform could be used for discovery of new communication systems not only in phages, but also in bacteria. In the second major aim of this project, we plan to apply our platform on the thousands of Gram positive bacteria available in the public databases in attempt to massively uncover and validate new µ-proteins that direct bacterial communication.

在每一次感染中，温和的寄生虫都需要决定是复制并裂解宿主，还是溶原化并保持宿主的活力。作为当前SPP 2002优先计划的第一期的一部分，我们发现感染芽孢杆菌的芽孢杆菌使用小分子通讯系统来协调裂解-溶原性决定（Erez等人，Nature 2017; Stokar-Avihail等人，Cell Host & Microbe 2019）。在感染宿主细胞的过程中，噬菌体产生一个短的（6aa-10aa）通讯肽，由μ蛋白产生并释放到培养基中。在随后的感染中，子代噬菌体测量该肽的浓度，如果浓度足够高，则进行溶原化。我们把这种制度称为“仲裁”制度（拉丁文的“决定”）。我们的研究结果表明，许多寄生虫携带仲裁编码μ蛋白，并使用它们来沟通和协调感染决策。然而，到目前为止，所有arbitrium同系物中发现的原噬菌体驻留在细菌基因组属于分类家庭芽孢杆菌科，目前尚不清楚是否感染细菌的其他分类组也利用基于肽的通信策略裂解/溶原性的决定。在目前的项目中，我们将试图发现额外的，arbitrium-like系统的细菌感染的非芽孢杆菌物种。由于arbitrium系统的发现形成了病毒之间实际交流的第一个证明，它代表了病毒学的一个新范式，可能会超越原核世界。了解噬菌体通讯系统的多样性和局限性不仅有助于我们为细菌和噬菌体基因组中的数百种μ蛋白分配功能，作为SPP 2002前三年的一部分，我们开发了一个通用平台，用于计算发现和实验验证μ-蛋白质，基于数千个感兴趣的基因组的通信系统。我们表明，这个平台不仅可以用于在细菌中发现新的通信系统，还可以用于在细菌中发现新的通信系统。在该项目的第二个主要目标中，我们计划将我们的平台应用于公共数据库中的数千种革兰氏阳性细菌，试图大规模发现和验证指导细菌通讯的新μ蛋白。