PDF (Published version) 128692.pdf | Download (652kB)

Abstract

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a singleinfectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lunghas evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosisinfection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The developmentof resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistanttuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. Forinstance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequentlytransformed into their active form by components of the OS responses of both host (nitric oxide, S-oxidation) and pathogen(catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in thehost, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin,superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation ofantitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptibleand drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standardantitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host’s OS response.

Item Type:	Article
Authors/Creators:	Shastri, MD and Shukla, SD and Chong, WC and Dua, K and Peterson, GM and Patel, RP and Hansbro, PM and Eri, R and O'Toole, RF
Keywords:	Mycobacterium tuberculosis, oxidative stress, isoniazid, ethionamide
Journal or Publication Title:	Oxidative Medicine and Cellular Longevity
Publisher:	Hindawi Publishing Corporation
ISSN:	1942-0900
DOI / ID Number:	https://doi.org/10.1155/2018/7695364
Copyright Information:	© 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Related URLs:	UTAS Profile: Shastri, MD UTAS Profile: Peterson, GM UTAS Profile: Patel, RP Google Scholar: Eri, R UTAS Profile: Eri, R Google Scholar: O'Toole, RF UTAS Profile: O'Toole, RF
Item Statistics:	View statistics for this item

Actions (login required)

Item Control Page