Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species

Mehta, Mansi and Singh, Amit (2019) Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species. In: FREE RADICAL BIOLOGY AND MEDICINE, 131 . pp. 50-58.

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Abstract

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 Mtb Delta whiB3 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, Mtb.whiB3 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.

Item Type:	Journal Article
Publication:	FREE RADICAL BIOLOGY AND MEDICINE
Publisher:	ELSEVIER SCIENCE INC
Additional Information:	Copyright of this article belongs to ELSEVIER SCIENCE INC
Keywords:	NITRIC-OXIDE; TRANSCRIPTIONAL REGULATOR; PEROXYNITRITE; RESISTANCE; VIRULENCE; GRANULOMA; REGULON; ACID; IDENTIFICATION; DISSEMINATION
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	06 Feb 2019 05:05
Last Modified:	18 Jun 2019 07:26
URI:	http://eprints.iisc.ac.in/id/eprint/61580

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