WhiB6 Differentially Regulates ESX-1 and Dos Regulon to Modulate Transition between Resuscitation and Dormancy during Mycobacterial Infection

During the course of infection Mycobacterium tuberculosis (Mtb) is exposed to diverse redox stresses that trigger metabolic and physiological changes. However, how these stressors are sensed and relayed to the Mtb transcriptional apparatus is poorly understood.Here we provide in vivo evidence that WhiB6 differentially regulates ESX-1 and DosR using its Fe-S cluster.Comparative transcriptomic analysis of the holo- and reduced apo-WhiB6 complemented strains not only confirms these results, but also reveals that WhiB6 controls aerobic and anaerobic metabolism, cell division as well as virulence.These findings offer fresh insight into how WhiB6 regulates the transition between dormancy and resuscitation during mycobacterial infection.