mycobacterium tuberculosis transcriptional adaptation, growth arrest and dormancy phenotype development is triggered by vitamin c结核分枝杆菌转录适应、成长逮捕和休眠表型发展是由维生素c.pdfVIP

Mycobacterium tuberculosis Transcriptional Adaptation, Growth Arrest and Dormancy Phenotype Development Is Triggered by Vitamin C 1 1 2 3 1 Neetu Kumra Taneja , Sakshi Dhingra , Aditya Mittal , Mohit Naresh , Jaya Sivaswami Tyagi * 1 Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India, 2 School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India, 3 Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India Abstract Background: Tubercle bacilli are thought to persist in a dormant state during latent tuberculosis (TB) infection. Although little is known about the host factors that induce and maintain Mycobacterium tuberculosis (M. tb) within latent lesions, O2 depletion, nutrient limitation and acidification are some of the stresses implicated in bacterial dormancy development/ growth arrest. Adaptation to hypoxia and exposure to NO/CO is implemented through the DevRS/DosT two-component system which induces the dormancy regulon. Methodology/Principal Findings: Here we show that vitamin C (ascorbic acid/AA) can serve as an additional signal to induce the DevR regulon. Physiological levels of AA scavenge O2 and rapidly induce the DevR regulon at an estimated O2 saturation of ,30%. The kinetics and magnitude of the response suggests an initial involvement of DosT and a sustained DevS-mediated response during bacterial adaptation to increasing hypoxia. In addition to inducing DevR regulon mechanisms, vitamin C induces the expression of selected genes previously shown to be responsive to low pH and oxidative stress, triggers bacterial growth arrest