The primary goal of the research is to identify the FT and BP genes responsible for several intrinsic antibiotic resistance, virulence and stress tolerance traits. The results should provide mechanistic insights into the physiological basis of each and may identify potential antibacterial drug targets. An additional set of experiments will help define BP species diversity in these and other phenotypes, and may identify diagnostic tests to differentiate natural isolates. As part of the project, a new-generation sequencing-based technology for assessing the makeup of transposon mutant pools of will be developed.
1. Functions required for intrinsic antibiotic resistance and stress resistance are potential drug targets for combination antibacterial therapy. We anticipate that conserved homeostatic functions will be represented and may represent broad host range targets. 2. The analysis of B. pseudomallei phenotypic species variation may identify diagnostic growth tests for discriminating rapidly between natural (non-laboratory) isolates. 3. The F. novicida mutant-phenotype database to be constructed should eventually serve as a reference for identifying the mechanisms of action of new antibacterial compounds (chemogenomic profiling), including those active against a broad range of organisms.
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