Temperate Bacteriophages Manipulate Bacterial Populations

背景：噬菌体是感染细菌的病毒。它们无处不在，数量丰富（数量超过宿主细菌，10:1），据估计每天杀死所有细菌的20-40% (3)！以一种类似于捕食者的方式，它们在形成微生物群落方面起着关键作用(5)。通过类比一个更熟悉的捕食者的生态影响，黄石国家公园是一个更健康和稳定的生态系统，因为狼的重新引入(6)。噬菌体还对细菌施加另一种非常不同的控制形式。一些被称为温带噬菌体，在宿主体内进入休眠状态，直到条件有利于它们的唤醒（诱导）。这些休眠的噬菌体极大地改变了它们所感染细菌的生理机能，赋予其他噬菌体免疫力（32），编码新的功能（34），并为被感染的细胞提供一些适应性益处（36）。

Background: Bacteriophages (phages) are viruses that infect bacteria. They are ubiquitous, abundant, (outnumbering their hosts, bacteria, 10:1), and are estimated to kill 20-40% of all bacteria every day (3)! In a manner akin to predators, they play a critical role in shaping microbial communities (5). By analogy to a more familiar predator's ecological impact, Yellowstone National Park is a healthier and more stable ecosystem since the re-introduction of wolves (6). Phages also exert another very different form of control over bacteria. Some, known as temperate phages, enter a dormant state within the host until conditions favour their awakening (induction). These dormant phages drastically alter the physiology of the bacteria they infect, conferring immunity to other phages (32), encoding new functions (34), and providing some fitness benefits to infected cells (36). Due to ease of discovery as well as their therapeutic potential, there has been a bias towards the study of virulent (non-temperate) phages. Temperate phages are understudied, but far more common, comprising the majority of phages in more stable microbial communities such as that of the human gut (7). Their ability to both kill and directly benefit their hosts make these phages particularly interesting. Vision: Determine the role of temperate phages in shaping stable microbial populations. Approach: Find new phages. I have access to a large collection of previously unculturable gut microbiome isolates. This will serve as the target for isolation of new phages and identification of new signals capable of inducing (awakening) phages from gut bacteria. Assess their impact on their host. Hypothesis: Phage-carrying cells are generally fitter than their phage-free counterparts. By competing infected and uninfected bacteria and observing their phenotypes, I will identify how each new temperate phage is affecting its bacterial host's physiology. Probe phage-containing bacterial communities. Hypothesis: Bacterial communities with temperate phages are more stable. I will create model microbial populations which include phages. This will then allow me to manipulate the environment and the phages in order to observe the effects of those perturbations on the community as a whole. Impact: Phages are master manipulators of bacteria. Isolating new phages is bound to uncover phage-derived tools to manipulate bacteria, much as it has in the past (e.g. anti-CRISPRs, T4 DNA ligase). Furthermore, temperate phages themselves can serve as a non-GMO means to improve the fitness of bacteria used in processes such as bioremediation, biofertilization and bacterial fermentations. Lastly, understanding the role of phages in shaping microbial communities as well as identifying factors that can trigger their phage-driven perturbation/stabilization will aid us in creating stable complex bacterial mixes for biotechnological applications.