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Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis

Citation

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, Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis, Oxidative Medicine and Cellular Longevity, 2018 Article 7695364. ISSN 1942-0900 (2018) [Refereed Article]


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© 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1155/2018/7695364

Abstract

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequently transformed 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 the host, 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 of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptible and drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the hostís OS response.

Item Details

Item Type:Refereed Article
Keywords:Mycobacterium tuberculosis, oxidative stress, isoniazid, ethionamide
Research Division:Medical and Health Sciences
Research Group:Medical Microbiology
Research Field:Medical Bacteriology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
Author:Shastri, MD (Mr Madhur Shastri)
Author:Peterson, GM (Professor Gregory Peterson)
Author:Patel, RP (Dr Rahul Patel)
Author:Eri, R (Associate Professor Raj Eri)
Author:O'Toole, RF (Dr Ronan O'Toole)
ID Code:128692
Year Published:2018
Deposited By:Medicine (Discipline)
Deposited On:2018-10-07
Last Modified:2018-11-28
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