appropriate devr (dosr)-mediated signaling determines transcriptional response, hypoxic viability and virulence of mycobacterium tuberculosis适当的devr(dosr)介导的信号决定转录反应,缺氧生存能力和结核分枝杆菌的毒性.pdf

Appropriate DevR (DosR)-Mediated Signaling Determines Transcriptional Response, Hypoxic Viability and Virulence of Mycobacterium tuberculosis 1 1 1 1 1¤ 2 Shyamasree De Majumdar , Atul Vashist , Sakshi Dhingra , Rajesh Gupta , Alka Singh , Vijay K. Challu , 3 2 1 V. D. Ramanathan , Prahlad Kumar , Jaya Sivaswami Tyagi * 1 Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India, 2 National Tuberculosis Institute, Bangalore, India, 3 Department of Pathology, Tuberculosis Research Centre, Chennai, India Abstract Background: The DevR(DosR) regulon is implicated in hypoxic adaptation and virulence of Mycobacterium tuberculosis. The present study was designed to decipher the impact of perturbation in DevR-mediated signaling on these properties. Methodology/Principal Findings: M. tb complemented (Comp) strains expressing different levels of DevR were constructed in Mut1* background (expressing DevR N-terminal domain in fusion with AphI (DevRN-Kan) and in Mut2DdevR background (deletion mutant). They were compared for their hypoxia adaptation and virulence properties. Diverse phenotypes were noted; basal level expression (,5.362.3 mM) when induced to levels equivalent to WT levels (,25.869.3 mM) was associated with robust DevR regulon induction and hypoxic adaptation (Comp 9* and 10*), whereas low-level expression (detectable at transcript level) as in Comp 11* and Comp15 was associated with an adaptation defect. Intermediate-level expression (,3.361.2 mM) partially restored hypoxic adaptation functions in Comp2, but not in Comp1* bacteria that co- exp