Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery

Iqbal, Iram and Bajeli, Sapna and Akela, Ajit and Kumar, Ashwani (2018) Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery. Pathogens, 7 (1). p. 24. ISSN 2076-0817

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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.

Item Type: Article
Additional Information: Copyright of this article belongs to MDPI AG.
Uncontrolled Keywords: Mycobacterium tuberculosis; Q203; SQ109; antimycobacterials; bedaquiline; bioenergetics; drugs; electron transport chain; oxidative phosphorylation
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 27 Mar 2018 04:53
Last Modified: 20 Mar 2019 12:12

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