RESEARCH ARTICLE In-Vivo Gene Signatures ofMycobacterium tuberculosis in C3HeB/FeJ Mice

Despite considerable progress in understanding the pathogenesis ofMycobacterium tuber-culosis (Mtb), development of new therapeutics and vaccines against it has proven difficult. This is at least in part due to the use of less than optimal models of in-vivo Mtb infection, which has precluded a study of the physiology of the pathogen in niches where it actually persists. C3HeB/FeJ (Kramnik) mice develop human-like lesions when experimentally infected withMtb and thus make available, a faithful and highly tractable system to study the physiology of the pathogen in-vivo. We compared the transcriptomics ofMtb and vari-ous mutants in the DosR (DevR) regulon derived from Kramnik mouse granulomas to those cultured in-vitro. We recently showed that mutant ΔdosS is attenuated in C3HeB/FeJ mice. Aerosol exposure of mice with the mutant mycobacteria resulted in a substantially different and a relatively weaker transcriptional response (< = 20 genes were induced) for the func