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Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery

Council of Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pathogens 2018, 7(1), 24; https://doi.org/10.3390/pathogens7010024
Received: 11 January 2018 / Revised: 29 January 2018 / Accepted: 31 January 2018 / Published: 23 February 2018
(This article belongs to the Special Issue Mechanisms of Mycobacterium tuberculosis Pathogenesis)
Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail. View Full-Text
Keywords: Mycobacterium tuberculosis; bioenergetics; oxidative phosphorylation; antimycobacterials; drugs; bedaquiline; Q203; SQ109; electron transport chain Mycobacterium tuberculosis; bioenergetics; oxidative phosphorylation; antimycobacterials; drugs; bedaquiline; Q203; SQ109; electron transport chain
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Iqbal, I.K.; Bajeli, S.; Akela, A.K.; Kumar, A. Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery. Pathogens 2018, 7, 24.

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