Historically, the study of animal associated microbes has focused on those rare examples that lead to disease. However, in recent decades, scientist and the public have come to recognize the importance of normal microflora to our health and development. For example, non-pathogenic bacteria aid in the development of a healthy immune system, and intimately associated gut commensals contribute to proper adsorption of nutrients. Despite the fact that such interactions are ubiquitous, little is known about how normal bacteria establish populations in association with hosts and are allowed to continue in association, without removal by the normal immune mechanisms that recognize and prevent bacterial infections. The study of normal bacterial interactions is also complicated by the fact that many commensal populations are comprised of complex communities of bacteria, some of which are uncultured. The goal of this research is to elucidate how normal bacteria colonize and maintain a host-associated population. This research focuses on beneficial host-microbe interactions using as a model the symbiosis between the bioluminescent bacterium Vibrio fischeri and the light organ of its animal host the squid Euprymna scolopes. This symbiosis serves as a simplified but natural model for understanding normal animal-microbe interactions, which are ubiquitous and yet underrepresented in research. Only V. fischeri can successfully navigate host defenses to colonize its nascent light organ. This association requires changes in and accommodation by both partners. During the process of colonization, the bacterium uses a two-component regulatory system, GacS/GacA, to globally control the expression of traits that allow it to adapt from a free-living to a host-associated lifestyle. Because this regulator coordinates the colonization process, its study will provide valuable information about the traits required to successfully initiate a benign infection. The study will include a genomic approach of microarray analysis, allowing the simultaneous study of hundreds of genes influenced by this regulator. The study will also include traditional mutagenesis to dissect key aspects of host association. Ultimately, these studies will elucidate mechanisms of beneficial bacterial-host association, providing new opportunities to exploit these relationships for enhanced health.
