We study the role that a group of bacterial genetic elements called toxin-antitoxin systems play in phage defense. We recently discovered that the DarTG toxin-antitoxin family provides robust defense against phage. We use this system, in which the toxins are DNA ADP-ribosyltransferases, as a model to answer fundamental questions about how toxin-antitoxin systems function as phage defense elements, e.g. how they sense phage infection, how toxins shut down virus replication, and how different growth conditions affect defense function.

Due to the growing rise of antibiotic resistance, there is increased interest in the use of phage to treat bacterial infections. One hurdle facing phage therapy is the existing bacterial immune system. Phage defense is not well understood in the pathogens that are the primary targets of phage therapy. Our lab performs screens to discover new phage defense pathways in opportunistic pathogens such as Pseudomonas aeruginosa. We also study how some phage have evolved to overcome bacterial defenses. These studies will ultimately inform the design and implementation of phage therapy.

Phage and bacteria are typically studied under standard laboratory conditions in which a single bacterial strain is grown with a single phage in rich growth media. In reality, bacteria are often surrounded by numerous phage, other bacterial species, associated with eukaryotic cells, encased in extracellular matrices called biofilms, and/or contending with antibiotics. We try to understand how such diverse environmental conditions affect phage-bacterial interactions. These studies will allow more accurate predictions about how phage-bacterial interactions may play out in infections or other real-world scenarios.