The evolutionary repurposing of eukaryotic genes into bacterial effectors.

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In order to survive inside host cells, intracellular pathogens have evolved arsenals of effector proteins that manipulate host processes to create a replicative niche. One of the most extensive arsenals is maintained by Legionella pneumophila, an intracellular bacterium that persists in nature by growing within a wide range of freshwater protozoa. The objective of my research program is to understand how L. pneumophila commandeers and repurposes eukaryotic genes into bacterial effectors. With a remarkably large cohort of over 300 translocated effectors and several easily cultivatable hosts, Legionella represents an unparalleled experimental model system to probe fundamental mechanisms of effector evolution. Many Legionella effectors contain eukaryotic-like domains, suggesting they may be the product of interdomain horizontal gene transfer. Little is known about the evolutionary path that leads from protozoan gene to a bona fide Legionella effector targeting host processes. Building on my lab's demonstrated expertise in bacterial genomics and experimental evolution, we will map where Legionella's large arsenal of effectors came from, how new effectors can be acquired, and what evolutionary processes support the functional transition of horizontally acquired genes into bona fide translocated effectors.While other studies have focused on the biochemical activity of isolated Legionella effectors, the confluence of several technologies has placed previously intractable but long outstanding questions about effector origin and evolution within our reach. Using comparative genomics, transcriptional profiling, and experimental evolution, we will uncover the fundamental processes that continue to shape the ecological niche and host range of these environmentally ubiquitous bacteria. We anticipate that these studies will provide broad foundational insight into the evolutionary repurposing of genes acquired through horizontal gene transfer, a critical contributor to bacterial evolution.