Bacterial pathogens are diverse and important enemies of plants. In agriculture, these pathogens cause significant destruction of crops and necessitate costly applications of antibiotics. How is it that wild plants are able to resist infection by these same bacteria? If the resistance mechanisms of wild plants can be identified, they can be used to improve the resistance of crops. Towards this goal, this research team has discovered that some wild collected plants of Arabidopsis thaliana are dramatically more resistant to infection by the virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000. The focus of the current project is to understand how elevated resistance in these plants is accomplished. For this purpose, the researchers use a powerful new approach, genome-wide association mapping, combined with mining of microarray data on gene expression, to identify focal candidate genes. RNAi knockdown lines will be created for these focal genes in the Stewart Lab and characterized in the Traw Lab for defects in plant resistance. In addition, plants lacking functional copies of these genes will be complemented with resistance allele candidates in both labs and tested in the Traw Lab to determine whether resistance is restored to those lines. Finally, given suspected roles of several candidates in membrane transport, broad and focused metabolite screening will be conducted by the Traw Lab using a subset of the experimental lines. One of the novel candidate genes is involved in the downstream response to abscisic acid. Allelic variation at that locus may therefore help explain how this bacterial pathogen is able to hijack the abscisic acid pathway in some plants. Thus, the project will provide strong insights into the mechanisms of natural plant resistance to bacteria. The findings are likely to contribute to the improvement of crop yields and reduction of exogenous antibiotic use in agriculture. The research may also contribute to improved treatment of bacterial diseases in humans. The project will advance the training of two postdocs and a graduate student, and will be used to create a series of laboratories that can be used in the teaching of introductory biology.