How bacteriophage kill bacteria

Bacteriophage, also known as phage, are ubiquitous in the natural world as predators and modulators of environmental biomass cycling. At the cellular level, these bacterial viruses specifically recognize and infect their preferred host cells, turning them into phage replication factories. After a genetically defined period of time, phage progeny escape from infected host cells in a lethal lysis event. Phage research laid the foundations of modern molecular biology and they remain useful tools teaching us about the principles that govern cellular life. Since developing the methods to isolate phage over a century ago, humanity has been attempting to harness them as reliable therapeutics to kill their bacterial hosts. In the post-antibiotic era, the concept of phage therapy broadly applied has the potential to help us control pesky bacteria, including antibiotic-resistant pathogens, in a variety of contexts. To make this a reality, we need careful characterization of many phage varieties by scientists and open communication with stakeholders in many industries.

Underpinning our explorations of applied phage biology are the basic science programs studying the biochemical mechanisms, genetic diversity, and regulatory pathways that govern phage cell-killing capabilities. In the Ramsey lab, we will use molecular virology and genomic tools in both phage newly isolated from the environment and model phage systems to answer fundamental questions about how phage kill bacteria. We will approach this from several angles to learn about the role of phage proteins, factors that influence phage-host interactions, and how conserved those mechanisms are across phage and their hosts. What we learn from these fundamental studies of bacteriophage and bacterial cell biology can help scientists and physicians that aim to kill bacteria in clinical or commercial settings.

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