We explore the interplay between bacteriophages, phage resistance mechanisms, ecology, and evolution. We aim to apply insights from our work to assist in the fight against antibiotic resistance in bacterial pathogens.
- Regulation and evolution of anti-phage defense systems: Bacteria have evolved a vast array of defense mechanisms to protect themselves against infection by mobile genetic elements, such as bacteriophages (phages) and plasmids. Some notable examples include CRISPR-Cas loci, abortive infection mechanisms, and restriction modification. However, mobile genetic elements are also crucial for bacterial evolution and adaptability, acting as key mediators of horizontal gene transfer. Thus, we are interested in how anti-phage defense systems mediate defense versus acquisition of mobile genetic elements. Research projects include:
- Bacterial and phage transcription factors that modulate anti-defense mechanisms.
- Evolution of defense systems and their surrounding genes.
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Genetic trade-offs of phage resistance mechanisms: Phage resistance is associated with genetic trade-offs in antibiotic resistance and virulence across many bacterial species. For example, the evolution of phage resistance in methicillin-resistant Staphylococcus aureus (MRSA) resulted in up to a 1000-fold reduction of resistance against beta-lactams, re-sensitizing the cells to antibiotics against which they were previously resistant (Tran*, Hernandez Viera* et al., eLife 2025). We are interested in elucidating the mechanisms of these phage-driven trade-offs and harnessing them for biomedical purposes. Research projects include:
- High-throughput screening for phage resistance trade-offs.
- Mechanistic characterization of how trade-offs work.
- Examining how phage resistance trade-offs affect pathogen interactions with the immune system.
- Phage infection in poly-microbial communities: Most bacteria exist within diverse poly-microbial communities, and interactions between community members produce unique evolutionary and ecological outcomes. The prevailing assumption is that in these communities, phages target their specific host species, while leaving the other non-host species unperturbed. This picture is likely more complex, as interactions between different community members can change a species’ susceptibility to viral infection. To study how the ecological interactions between bacteria impact resistance evolution, we are investigating phage resistance in multi-species communities including the pathogens MRSA and Pseudomonas aeruginosa. This work represents an important step in the pathway from single-species evolution studies to more naturalistic experimental systems, and eventually, successful phage therapies.