Temperate Bacteriophages Manipulate Bacterial Populations

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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.