Mycobacterium tuberculosis MT2816 encodes a key stress-response regulator

Background: Sigma (σ) factors are transcription initiation factors that modulate the response of Mycobacterium tuberculosis to changes in extracellular milieu, allowing it to survive stress. Methods: We analyzed the expression of MT2816/Rv2745c under various stress conditions that mimic the intracellular environment faced by M. tuberculosis. Results: MT2816/Rv2745c expression was induced in M. tuberculosis following redox stress, heat shock and acid shock and intracellular replication. Its expression was also induced by SDS and thioridazine, agents that impact M. tuberculosis cell-envelope. However, exposure to isoniazid or ethambutol, front-line antituberculosis drugs which also target the cell envelope, did not induce the expression of MT2816/Rv2745c. Studies using Δ-σ^H and Δ-σ^E mutants showed that Δ^H was required for the induction of MT2816/Rv2745c. Conditional expression of the MT2816/Rv2745c in M. tuberculosis showed that apart from regulating proteolysis, this gene may control the expression of trehalose biosynthesis and impact the maintenance of cellular redox potential and energy generation. Conclusions: The protein encoded by MT2816/Rv2745c is important for the pathogen's response to stress conditions that mimic in vivo growth and it is subject to complex regulation. The MT2816/Rv2745c encoded protein likely functions by protecting intracellular redox potential and by inducing the expression of trehalose, a constituent of M. tuberculosis cell walls that is important for defense against cell-surface and oxidative stress.