Chemical warfare in the phage-host evolutionary arms race

The battle for survival between bacteria and the viruses that infect them, known as phages, has led to the evolution of a wide range of anti-phage defences. These include cell surface modifications, restriction enzymes, abortive infection systems, and the CRISPR-Cas adaptive immune system. While these defence systems are highly varied mechanistically, they all rely on proteins or protein-RNA complexes to mediate their functions. We recently discovered a new anti-phage defence system based on the production of small molecules known as secondary metabolites. This chemical defence directly targets the phage genome upon infection, and broadly inhibits most phages. Chemical defence is also provided indirectly in some bacteria through quorum-mediated control of protein-based anti-phage defences. In response, phages have evolved diverse inhibitors that short-circuit these protective defence pathways. Work in our lab is aimed at characterizing these pathways to provide insight into the complex interplay between bacteria and their most fearsome predators.