The Microbial Battlefield: Streptomyces Anti-Phage Chemical Warfare

微生物战场：链霉菌抗噬菌体化学战

• 批准号: RGPIN-2017-06898
• 负责人: Maxwell, Karen
• 金额: $ 2.04万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=659092
• 关键词: Microbial; Battlefield; Streptomyces; Anti; Phage

This grant will investigate the production of anti-phage secondary metabolites by Streptomyces bacteria. Phages are viruses that infect and kill bacteria. They are the most abundant biological entity on earth, outnumbering bacteria by a factor of ten. It is estimated that Avogadro's number of phage infections occurs each second on earth. This pervasive selection pressure combined with the ubiquity of phages in the environment has led to the evolution of a wide array of bacterial anti-phage defense mechanisms. For example, bacteria can inhibit phage attachment at the cell surface, block genome replication, or degrade the phage genome using restriction enzymes or the CRISPR-Cas system. Given the intensity of the bacteria-phage arms race, it is highly probable that other defense mechanisms remain to be delineated. Characterization of these mechanisms will provide important insight into how phage-host interactions shape the microbial world. ******Previous studies searching for compounds that inhibit E. coli phage replication identified a number of secondary metabolites produced by different species of Streptomyces that actively block phage propagation. The high frequency with which we identified these secondary metabolites among Streptomyces strains led us to hypothesize that secondary metabolites provide a previously uncharacterized anti-phage defense system. In this proposal, we will determine if Streptomyces use secondary metabolites as an endogenous anti-phage defense mechanism and will identify genetic pathways through which these molecules are synthesized. We have developed a unique platform for pursuing these studies that combines high-throughput screening with detailed biochemical and genetic studies that will allow us to identify molecules and directly link them with anti-phage activities. This work will ascribe biological functions to previously uncharacterized secondary metabolites and provide new insight into the evolutionary arms race between bacteria and phages, which plays important roles in nutrient cycling, global climate, biodiversity, and species distribution.

该赠款将调查链霉菌细菌抗流量二级代谢产物的产生。噬菌体是感染和杀死细菌的病毒。它们是地球上最丰富的生物实体，人数超过十倍。据估计，Avogadro的噬菌体感染数量每秒发生在地球上。这种普遍的选择压力与环境中噬菌体无处不在的压力相结合，导致了各种各样的细菌抗流量防御机制的演变。例如，细菌可以抑制细胞表面的噬菌体附着，阻断基因组复制，或使用限制酶或CRISPR-CAS系统降解噬菌体基因组。鉴于细菌 - 旧武器竞赛的强度，很有可能会划定其他防御机制。这些机制的表征将为噬菌体 - 宿主相互作用如何塑造微生物世界提供重要的见解。 *********搜索抑制大肠杆菌噬菌体复制的化合物的研究确定了由不同种类的链霉菌物种产生的许多二级代谢产物，这些代谢产生了积极阻止噬菌体传播的链霉菌。我们在链霉菌菌株中确定这些二级代谢物的高频导致我们假设次级代谢产物提供了先前未表征的抗衰弱防御系统。在此提案中，我们将确定链霉菌是否使用二级代谢产物作为内源性抗流量防御机制，并将确定这些分子合成的遗传途径。我们开发了一个独特的平台来进行这些研究，将高通量筛查与详细的生化和遗传研究相结合，这将使我们能够识别分子并将其直接与抗流量活动联系起来。这项工作将生物学功能归因于先前未表征的二级代谢产物，并为细菌与噬菌体之间的进化武器竞赛提供新的见解，这在营养循环，全球气候，生物多样性和物种分布中起着重要作用。