Transcriptional adaptation of that survives prolonged multi-drug treatment in mice.

A major reason that curing tuberculosis requires prolonged treatment is that drug exposure changes bacterial phenotypes. The physiologic adaptations of that survive drug exposure have been obscure due to low sensitivity of existing methods in drug-treated animals. Using the novel SEARCH-TB RNA-seq platform, we elucidated phenotypes in mice treated for with the global standard 4-drug regimen and compared them with the effect of the same regimen . This first view of the transcriptome of the minority population that withstands treatment reveals adaptation of a broad range of cellular processes, including a shift in metabolism and cell wall modification. Surprisingly, the change in gene expression induced by treatment and was largely similar. This apparent "portability" from to the mouse provides important new context for transcriptional analyses that may support early preclinical drug evaluation.