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Targeting Energy Metabolism in , a New Paradigm in Antimycobacterial Drug Discovery. | LitMetric

Targeting Energy Metabolism in , a New Paradigm in Antimycobacterial Drug Discovery.

mBio

Infectious Diseases and Vaccines Therapeutic Area, Janssen Research & Development, Beerse, Belgium

Published: April 2017

AI Article Synopsis

  • Drug-resistant mycobacterial infections are a critical issue worldwide, causing high death rates and significant economic impacts, especially in developing countries.
  • New research is focusing on the energy metabolism of mycobacteria, particularly the oxidative phosphorylation pathway, as a promising target for developing innovative antibiotics.
  • Recent approvals of drugs like bedaquiline and the discovery of candidates like Q203 underscore the potential of this pathway in creating effective treatments for both regular and multidrug-resistant tuberculosis.

Article 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 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388804PMC
http://dx.doi.org/10.1128/mBio.00272-17DOI Listing

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