Targeting energy metabolism in Mycobacterium tuberculosis – a new paradigm in anti-mycobacterial drug discovery.

D. Bald, C. Villellas, P. Lu, A. Koul

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Drug-resistant mycobacterial infections are a serious global health challenge, leading to high mortality and socioeconomic burdens in developing countries worldwide. New innovative approaches, from identification of new targets to discovery of novel chemical scaffolds, are urgently needed. Recently, energy metabolism in mycobacteria, in particular the oxidative phosphorylation pathway, has emerged as an object of intense microbiological investigation and as a novel target pathway in drug discovery. New classes of antibacterials interfering with elements of the oxidative phosphorylation pathway are highly active in combating dormant or latent mycobacterial infections, with a promise of shortening tuberculosis chemotherapy. The regulatory approval of the ATP synthase inhibitor bedaquiline and the discovery of Q203, a candidate drug targeting the cytochrome bc1 complex, have highlighted the central importance of this new target pathway. In this review, we discuss key features and potential applications of inhibiting energy metabolism in our quest for discovering potent novel and sterilizing drug combinations for combating tuberculosis. We believe that the combination of drugs targeting elements of the oxidative phosphorylation pathway can lead to a completely new regimen for drug-susceptible and multidrug-resistant tuberculosis.
LanguageEnglish
Pages1-11
Number of pages11
JournalmBio
Volume8
Issue number2
DOIs
Publication statusPublished - 2017

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Oxidative Phosphorylation
Drug Discovery
Mycobacterium tuberculosis
Energy Metabolism
Drug Delivery Systems
bedaquiline
Tuberculosis
Multidrug-Resistant Tuberculosis
Electron Transport Complex III
Drug Combinations
Mycobacterium
Infection
Pharmaceutical Preparations
Developing Countries
Adenosine Triphosphate
Drug Therapy
Mortality

Cite this

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title = "Targeting energy metabolism in Mycobacterium tuberculosis – a new paradigm in anti-mycobacterial drug discovery.",
abstract = "Drug-resistant mycobacterial infections are a serious global health challenge, leading to high mortality and socioeconomic burdens in developing countries worldwide. New innovative approaches, from identification of new targets to discovery of novel chemical scaffolds, are urgently needed. Recently, energy metabolism in mycobacteria, in particular the oxidative phosphorylation pathway, has emerged as an object of intense microbiological investigation and as a novel target pathway in drug discovery. New classes of antibacterials interfering with elements of the oxidative phosphorylation pathway are highly active in combating dormant or latent mycobacterial infections, with a promise of shortening tuberculosis chemotherapy. The regulatory approval of the ATP synthase inhibitor bedaquiline and the discovery of Q203, a candidate drug targeting the cytochrome bc1 complex, have highlighted the central importance of this new target pathway. In this review, we discuss key features and potential applications of inhibiting energy metabolism in our quest for discovering potent novel and sterilizing drug combinations for combating tuberculosis. We believe that the combination of drugs targeting elements of the oxidative phosphorylation pathway can lead to a completely new regimen for drug-susceptible and multidrug-resistant tuberculosis.",
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Targeting energy metabolism in Mycobacterium tuberculosis – a new paradigm in anti-mycobacterial drug discovery. / Bald, D.; Villellas, C.; Lu, P.; Koul, A.

In: mBio, Vol. 8, No. 2, 2017, p. 1-11.

Research output: Contribution to JournalArticleAcademicpeer-review

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