Analysis of a reaeration model of laten TB reactivation

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DESCRIPTION (provided by applicant): The goal of the proposed postdoctoral research is characterize the genetic program of reactivation from dormancy in Mycobacterium tuberculosis using an in vitro hypoxic model. The requirement for these genes in reactivation will be tested by mutagenesis and in vitro and in vivo phenotypic assessment. This investigation will improve our understanding of the bacterial physiology of M. tuberculosis in the latent state and subsequent reactivation. The specific aims of the project are: 1. To use an in vitro model to identify reactivation-specific genes using microarray analysis. 2. To identify genes essential for the transition from hypoxic dormancy to reaerated culture using transposon site hybridization (TraSH). 3. To isolate transposon mutants with insertions into predicted reactivation-specific genes and to test the requirement for these genes for reactivation in vitro and in a mouse model.