Regulation of Host Colonization Specificity

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Bacteria colonize and perform critical functions for their animal hosts. There has been an increased understanding of the bacteria that are associated with specific animal hosts, but the proceses and mechanisms by which specific animals become colonized with characteristic beneficial bacteria and avoid colonization by harmful (pathogenic) bacteria are not well-understood. This project uses a simplified system in which an animal organ is colonized by only a single bacterial species as a way to examine these processes and mechanisms. Molecular genetic approaches will be used to identify bacterial genes and processes that are critical to host colonization, and comparative approaches will be used to determine how the gene circuits in different bacteria evolve to either keep the same animal partner or allow the bacteria to switch and colonize a new animal host. This work has the potential to impact studies of bacterial aggregation, a process that occurs readily and has broad implications for the ability of bacteria to perform beneficial or harmful functions in natural and man-made environments. Climate change has been shown to influence bacterial-animal associations, so a deeper understanding of the molecular basis to these interactions will allow us to better prepare for changing environmental conditions. Finally, the evolution of infectious diseases depends on pathogen interactions with animal hosts, and therefore it is critical to discern regulatory changes that influence microbe-host communication. Students will be trained in modern genetics and genomics, and bioinformatics to address "big data" questions. Outreach activities are focused on broadening the representation of future STEM field leaders. Microbial symbioses are prevalent in animals and are crucial to the health and development of both partners. These relationships have evolved robust mechanisms to ensure the faithful transmission of symbionts during each new host generation. This project applies modern genomic and genetic methods to examine how host specificity develops in a horizontally transmitted animal-microbe symbiosis. The project focuses on the binary association between Vibrio fischeri bacteria and the bobtail squid hosts. Preliminary data have revealed the importance of biofilm formation (bacterial aggregation) during host colonization, both in V. fischeri colonization of squid and in many bacterial colonization systems. In the canonical squid symbiont ES114, the RscS histidine kinase activates biofilm genes that are necessary for normal host colonization. A comparative approach identified strains that do not use RscS for colonization, and in the project molecular genetic approaches will be undertaken to identify the signal transduction pathways regulating aggregation and colonization in closely related symbiont strains. By taking an integrative approach that encompasses natural populations, genomes, pathways, and genes, the project will yield an understanding of the molecular mechanisms that maintain symbiont-host fidelity and facilitate co-evolutionary dynamics in horizontally-transmitted bacterial symbionts. A pilot workshop is proposed that integrates with the research aims and trains undergraduate and graduate students in modern bioinformatics techniques.