We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species.
Free Radical Biology & Medicine 2019 Februrary 2
Mycobacterium tuberculosis (Mtb) survives under oxidatively and nitosatively hostile niches inside host phagocytes. In other bacteria, adaptation to these stresses is dependent upon the redox sensitive two component systems (e.g., ArcAB) and transcription factors (e.g., FNR/SoxR). However, these factors are absent in Mtb. Therefore, it is not completely understood how Mtb maintains survival and redox balance in response to reactive oxygen species (ROS) and reactive nitrogen species (RNS). Here, we present evidences that a 4Fe-4S-cofactor containing redox-sensitive transcription factor (WhiB3) is exploited by Mtb to adapt under ROS and RNS stress. We show that MtbΔwhiB3 is acutely sensitive to oxidants and to nitrosative agents. Using a genetic biosensor of cytoplasmic redox state (Mrx1-roGFP2) of Mtb, we show that WhiB3 facilitates recovery from ROS (cumene hydroperoxide and hydrogen peroxide) and RNS (acidified nitrite and peroxynitrite). Also, MtbΔwhiB3 displayed reduced survival inside RAW 264.7 macrophages. Consistent with the role of WhiB3 in modulating host-pathogen interaction, we discovered that WhiB3 coordinates the formation of early human granulomas during interaction of Mtb with human peripheral blood mononuclear cells (PBMCs). Altogether, our study provides empirical proof that WhiB3 is required to mitigate redox stress induced by ROS and RNS, which may be important to activate host/bacterial pathways required for the granuloma development and maintenance.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app