Hosts and pathogens are eternally intertwined in an evolutionary arms race. When a pathogen causes a disease outbreak, scientists must identify resistance strategies that can durably tilt the arms race in favor of the host. This requires a deep understanding of both the genetic and environmental contexts in which the outbreak occurs. In this thesis I investigate the bacterial pathogens Xanthomonas citri pv. malvacearum (Xcm) and Pseudomonas syringae that caused disease outbreaks on Gossypium hirsutum from 2011-2017. I use pathogen genomics and host transcriptomics to develop hypotheses for how these pathogens emerged and how they cause disease. Phylogenetics and virulence factor analysis reveal few differences between contemporary and historical isolates. Data on agricultural practices point to changing germplasm dynamics as a reason for disease re-emergence. These data led to a RNA-Seq experiment that identified several new candidate susceptibility genes including four SWEET sugar transporters and two Mildew Locus-O homologs that have been used to confer resistance to bacterial pathogens in other systems. As an alternative approach, a diversity panel of 52 cotton varieties was screened to reveal seven sources of resistance that can be used to prevent Xcm outbreaks in the future. While no resistance strategies have been identified for P. syringae, several virulence factors such as the type IV pilus and filamentous hemagglutinin were identified, which show evolutionary markers of a function in the host-pathogen arms race. These data are pivotal for determining the best strategies for developing durable host resistance strategies. Future work will focus on developing resistant varieties of cotton and performing reverse genetics to confirm the identities of virulence factors that contribute to pathogen fitness
