creators_name: Trivedi, Abhishek
creators_name: Singh, Nisha
creators_name: Bhat, Shabir Ahmed
creators_name: Gupta, Pawan
creators_name: Kumar, Ashwani
type: book_section
datestamp: 2013-01-28 11:29:55
lastmod: 2013-01-28 11:29:55
metadata_visibility: show
title: Redox biology of tuberculosis pathogenesis.
ispublished: pub
subjects: R1
keywords: Redox homeostasis;Virulence;Pathogenesis;DosR;WhiB3;  Metabolic flexibility; Mycothiol;Thioredoxin;Protective enzymes
note: Copyright of this article belongs to Elsevier Science.
abstract: Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens. Mtb is persistently exposed to numerous oxidoreductive stresses during its pathogenic cycle of infection and transmission. The distinctive ability of Mtb, not only to survive the redox stress manifested by the host but also to use it for synchronizing the metabolic pathways and expression of virulence factors, is central to its success as a pathogen. This review describes the paradigmatic redox and hypoxia sensors employed by Mtb to continuously monitor variations in the intracellular redox state and the surrounding microenvironment. Two component proteins, namely, DosS and DosT, are employed by Mtb to sense changes in oxygen, nitric oxide, and carbon monoxide levels, while WhiB3 and anti-sigma factor RsrA are used to monitor changes in intracellular redox state. Using these and other unidentified redox sensors, Mtb orchestrates its metabolic pathways to survive in nutrient-deficient, acidic, oxidative, nitrosative, and hypoxic environments inside granulomas or infectious lesions. A number of these metabolic pathways are unique to mycobacteria and thus represent potential drug targets. In addition, Mtb employs versatile machinery of the mycothiol and thioredoxin systems to ensure a reductive intracellular environment for optimal functioning of its proteins even upon exposure to oxidative stress. Mtb also utilizes a battery of protective enzymes, such as superoxide dismutase (SOD), catalase (KatG), alkyl hydroperoxidase (AhpC), and peroxiredoxins, to neutralize the redox stress generated by the host immune system. This chapter reviews the current understanding of mechanisms employed by Mtb to sense and neutralize redox stress and their importance in TB pathogenesis and drug development.
date: 2012
date_type: published
series: Advances in Microbial Physiology
publication: Advances in microbial physiology
volume: 60
number: 60
publisher: Elsevier Science
pagerange: 263-324
pages: 263
id_number: 10.1016/B978-0-12-398264-3.00004-8.
refereed: TRUE
issn: 0065-2911
book_title: Advances in Microbial Physiology
official_url: http://www.sciencedirect.com/science/bookseries/00652911/60/supp/C
citation:   Trivedi, Abhishek and Singh, Nisha and Bhat, Shabir Ahmed and Gupta, Pawan and Kumar, Ashwani  (2012) Redox biology of tuberculosis pathogenesis.   In:  Advances in Microbial Physiology.   Advances in Microbial Physiology, 60  (60).  Elsevier Science, pp. 263-324.