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-bacterial interactions are typically studied under standard laboratory conditions in model organisms such as Escherichia coli. Laboratory conditions may change many aspects of bacterial growth that could fundamentally affect their interactions with their viruses, and many of these behaviors are highly species specific. By thoughtfully varying the growth conditions to more closely mimic conditions found in natural settings, we are exploring how phage bacterial interactions are altered. We are also studying phage-bacterial interactions outside of E. coli to discover new types of defense pathways.