Transcriptome analysis of M.tuberculosis using RNA-seq indicates WhiB6 repression of dormancy associated genes. Mycobacterium tuberculosis CDC1551

Tuberculosis is an infectious disease, with latent infection with Mycobacterium tuberculosis (M.tb) affecting 1/3 of humanity. It can remain quiescent for long time, making eradication very difficult. To do so, M.tb need to carefully orchestrate its gene expression to survive immune response and starvation but still be able to reactivate to enable transmission to new hosts. Here we used whole transcriptome deep sequencing to compare gene expression between wild type M.tb and a strain with its whiB6, a gene encoding a putative redox-sensing transcription factor, disrupted by a transposon. We found several genes associated with dormancy such as hspX, fdxA and narK2 upregulated in the transposon mutant, indicating that WhiB6 may be a repressor of such genes. The results suggest that WhiB6 may be a complement to the dosS/dosR system in regulating genes important for dormancy. Overall design: Triplicate cultures of a mutant with its whiB6 gene disrupted by a transposon and wild-type M. tuberculosis CDC1551 were grown in 7H9 media. RNA was extracted and depleted from rRNA. Global gene expression was measured using AB SOLID RNA sequencing.