Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial 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....

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Autores principales:	Dirk Bald, Cristina Villellas, Ping Lu, Anil Koul
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	antibiotics Mycobacterium tuberculosis energy metabolism oxidative phosphorylation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/92755fb13b8648388e916f1c161fb33c
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spelling	oai:doaj.org-article:92755fb13b8648388e916f1c161fb33c2021-11-15T15:51:00ZTargeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery10.1128/mBio.00272-172150-7511https://doaj.org/article/92755fb13b8648388e916f1c161fb33c2017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00272-17https://doaj.org/toc/2150-7511ABSTRACT 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.Dirk BaldCristina VillellasPing LuAnil KoulAmerican Society for MicrobiologyarticleantibioticsMycobacterium tuberculosisenergy metabolismoxidative phosphorylationMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotics Mycobacterium tuberculosis energy metabolism oxidative phosphorylation Microbiology QR1-502
spellingShingle	antibiotics Mycobacterium tuberculosis energy metabolism oxidative phosphorylation Microbiology QR1-502 Dirk Bald Cristina Villellas Ping Lu Anil Koul Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery
description	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.
format	article
author	Dirk Bald Cristina Villellas Ping Lu Anil Koul
author_facet	Dirk Bald Cristina Villellas Ping Lu Anil Koul
author_sort	Dirk Bald
title	Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery
title_short	Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery
title_full	Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery
title_fullStr	Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery
title_full_unstemmed	Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery
title_sort	targeting energy metabolism in <italic toggle="yes">mycobacterium tuberculosis</italic>, a new paradigm in antimycobacterial drug discovery
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/92755fb13b8648388e916f1c161fb33c
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Targeting Energy Metabolism in <italic toggle="yes">Mycobacterium tuberculosis</italic>, a New Paradigm in Antimycobacterial Drug Discovery

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