Oxidative phosphorylation as a target space for tuberculosis: Success, caution, and future directions

Gregory M. Cook, Kiel Hards, Elyse Dunn, Adam Heikal, Yoshio Nakatani, Chris Greening, Dean C. Crick, Fabio L. Fontes, Kevin Pethe, Erik Hasenoehrl, Michael Berney

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


The emergence and spread of drug-resistant pathogens, and our inability to develop new antimicrobials to combat resistance, have inspired scientists to seek out new targets for drug development. The Mycobacterium tuberculosis complex is a group of obligately aerobic bacteria that have specialized for inhabiting a wide range of intracellular and extracellular environments. Two fundamental features in this adaptation are the flexible utilization of energy sources and continued metabolism in the absence of growth. M. tuberculosis is an obligately aerobic heterotroph that depends on oxidative phosphorylation for growth and survival. However, several studies are redefining the metabolic breadth of the genus. Alternative electron donors and acceptors may provide the maintenance energy for the pathogen to maintain viability in hypoxic, nonreplicating states relevant to latent infection. This hidden metabolic flexibility may ultimately decrease the efficacy of drugs targeted against primary dehydrogenases and terminal oxidases. However, it may also open up opportunities to develop novel antimycobacterials targeting persister cells. In this review, we discuss the progress in understanding the role of energetic targets in mycobacterial physiology and pathogenesis and the opportunities for drug discovery.

Original languageEnglish (US)
Article numberTBTB2-0014-2016
JournalMicrobiology Spectrum
Issue number3
StatePublished - Jun 1 2017

ASJC Scopus subject areas

  • Physiology
  • Ecology
  • General Immunology and Microbiology
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases


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