The role of small open reading frames in Shewanella oneidensis phage LambdaSo in host takeover and phage proliferation

噬菌体是捕食细菌的病毒。它们在自然界中惊人地丰富，影响着细菌的生态，包括所有元素循环或人类的微生物群。通常，噬菌体-宿主相互作用以两种主要方式发生。在裂解噬菌体周期中，噬菌体附着在宿主上，噬菌体染色体被运送到宿主细胞中。在那里，主要的细胞功能被接管，并被重定向到产生新的噬菌体颗粒，然后在宿主细胞裂解和死亡时释放出来。相比之下，溶原噬菌体能够在宿主细胞中稳定地建立染色体作为噬菌体，然后在细胞分裂期间繁殖噬菌体基因组。在某些信号，如细胞应激增加时，噬菌体被激活，其裂解周期被触发，导致噬菌体颗粒的产生并通过细胞裂解释放。在数十亿年的共同进化中，宿主和噬菌体已经进化出了大量的攻击和防御机制，其中大部分仍然是未知的，这也是由于大量未表征的噬菌体。在这个拟议的项目中，我们的目标是深入表征小噬菌体效应蛋白，这些蛋白允许希瓦氏菌的宿主接管和溶原LambdaSo噬菌体的增殖。我们将使用广泛的遗传学，蛋白质生物化学和荧光显微镜来了解两种小蛋白质如何能够接管宿主的细胞生长和分裂，以及控制终端细胞裂解和噬菌体释放。我们期望这些结果将对噬菌体影响宿主基本功能的过程提供根本性的新见解。

Phages are viruses that prey on bacteria. They are amazingly abundant in nature and affect the ecology of bacteria including all elemental cycles or the microbiome of humans. Generally, phage-host interaction occurs in two major fashions. In the lytic phage cycle, the phage attaches to its host and the phage chromosome is transported into the host cell. There, major cell functions are taken over and are redirected towards the production of novel phage particles, which are then released upon lysis -and death- of the host cell. In contrast, lysogenic phages are able to stably establish the chromosome as a prophage in the host cell, which will then propagate the phage genome during cell division. Upon certain signals, such as increased cell stress, the prophage is activated and its lytic cycle is triggered, leading to production of phage particles and their release by cell lysis. In billions of years of co-evolution, host and phages have evolved a huge amount of attack and defense mechanisms, most of which are still unknown, also due to the large number of uncharacterized phages. In this proposed project we are aiming at the in-depth characterization of small phage effector proteins that allow host-takeover and proliferation of the lysogen LambdaSo phage of Shewanella oneidensis. We will use a broad array of genetics, protein biochemistry and fluorescence microscopy to understand how two small proteins are able to take over cell growth and division of the host as well as to control the terminal cell lysis and phage release. We expect that the results will give fundamentally novel insights into the processes phages use to affect their host’s elementary functions.