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Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria

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  • Authors: Gregory M. Cook1, Kiel Hards2, Catherine Vilchèze3, Travis Hartman4, Michael Berney5
  • Editors: Graham F. Hatfull6, William R. Jacobs Jr.7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: University of Otago, Department of Microbiology and Immunology, Dunedin, New Zealand; 2: University of Otago, Department of Microbiology and Immunology, Dunedin, New Zealand; 3: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; 4: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; 5: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; 6: University of Pittsburgh, Pittsburgh, PA; 7: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY
  • Source: microbiolspec June 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0015-2013
  • Received 26 April 2013 Accepted 06 August 2013 Published 06 June 2014
  • G.M. Cook, gregory.cook@otago.ac.nz
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  • Abstract:

    Mycobacteria inhabit a wide range of intracellular and extracellular environments. Many of these environments are highly dynamic, and therefore mycobacteria are faced with the constant challenge of redirecting their metabolic activity to be commensurate with either replicative growth or a nonreplicative quiescence. A fundamental feature in this adaptation is the ability of mycobacteria to respire, regenerate reducing equivalents, and generate ATP via oxidative phosphorylation. Mycobacteria harbor multiple primary dehydrogenases to fuel the electron transport chain, and two terminal respiratory oxidases, an -type cytochrome oxidase and a cytochrome -type menaquinol oxidase, are present for dioxygen reduction coupled to the generation of a proton motive force (PMF). Hypoxia leads to the downregulation of key respiratory complexes, but the molecular mechanisms regulating this expression are unknown. Despite being obligate aerobes, mycobacteria have the ability to metabolize in the absence of oxygen, and a number of reductases are present to facilitate the turnover of reducing equivalents under these conditions (e.g., nitrate reductase, succinate dehydrogenase/fumarate reductase). Hydrogenases and ferredoxins are also present in the genomes of mycobacteria, suggesting the ability of these bacteria to adapt to an anaerobic type of metabolism in the absence of oxygen. ATP synthesis by the membrane-bound FF-ATP synthase is essential for growing and nongrowing mycobacteria, and the enzyme is able to function over a wide range of PMF values (aerobic to hypoxic). The discovery of lead compounds that target respiration and oxidative phosphorylation in highlights the importance of this area for the generation of new frontline drugs to combat tuberculosis.

  • Citation: Cook G, Hards K, Vilchèze C, Hartman T, Berney M. 2014. Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria. Microbiol Spectrum 2(3):MGM2-0015-2013. doi:10.1128/microbiolspec.MGM2-0015-2013.

Key Concept Ranking

Two-Component Signal Transduction Systems
0.4385909
Type II NADH Dehydrogenase
0.43061358
0.4385909

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/content/journal/microbiolspec/10.1128/microbiolspec.MGM2-0015-2013
2014-06-06
2017-09-25

Abstract:

Mycobacteria inhabit a wide range of intracellular and extracellular environments. Many of these environments are highly dynamic, and therefore mycobacteria are faced with the constant challenge of redirecting their metabolic activity to be commensurate with either replicative growth or a nonreplicative quiescence. A fundamental feature in this adaptation is the ability of mycobacteria to respire, regenerate reducing equivalents, and generate ATP via oxidative phosphorylation. Mycobacteria harbor multiple primary dehydrogenases to fuel the electron transport chain, and two terminal respiratory oxidases, an -type cytochrome oxidase and a cytochrome -type menaquinol oxidase, are present for dioxygen reduction coupled to the generation of a proton motive force (PMF). Hypoxia leads to the downregulation of key respiratory complexes, but the molecular mechanisms regulating this expression are unknown. Despite being obligate aerobes, mycobacteria have the ability to metabolize in the absence of oxygen, and a number of reductases are present to facilitate the turnover of reducing equivalents under these conditions (e.g., nitrate reductase, succinate dehydrogenase/fumarate reductase). Hydrogenases and ferredoxins are also present in the genomes of mycobacteria, suggesting the ability of these bacteria to adapt to an anaerobic type of metabolism in the absence of oxygen. ATP synthesis by the membrane-bound FF-ATP synthase is essential for growing and nongrowing mycobacteria, and the enzyme is able to function over a wide range of PMF values (aerobic to hypoxic). The discovery of lead compounds that target respiration and oxidative phosphorylation in highlights the importance of this area for the generation of new frontline drugs to combat tuberculosis.

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FIGURE 1

Organization and components of the electron transport chain in mycobacteria. doi:10.1128/microbiolspec.MGM2-0015-2013.f1

Source: microbiolspec June 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0015-2013
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FIGURE 2

The core respiratory chain of mycobacteria and components upregulated under energy-limiting conditions. During exponential growth, mycobacteria use a classical respiratory chain composed of a type I NADH:menaquinone oxidoreductase (Nuo)succinate:menaquinone oxidoreductase 1 (SDH1), cytochrome supercomplex (Qcr-Cta), and FF ATPase. Menaquinone (MQ) is the only quinone present in mycobacterial membranes, and reverse electron transport driven by the PMF is proposed to facilitate the function of SDH1 and similar enzymes (see text). Components in light blue are upregulated in response to energy-limiting conditions ( 6 ). Catalysis and electron flow are indicated by arrows. Abbreviations: Cox, carbon monoxide dehydrogenase; Hyd, hydrogenase; DH, dehydrogenase; A, unidentified electron acceptor. doi:10.1128/microbiolspec.MGM2-0015-2013.f2

Source: microbiolspec June 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0015-2013
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FIGURE 3

The preferential respiratory chain of an oxygen-limited mycobacterial cell. Under low-oxygen conditions, a diverse response utilizing alternate electron donors and acceptors, energy-conserving enzymes, and a high-affinity terminal oxidase permits survival under hypoxic conditions. Components in red are upregulated under microaerobic conditions ( 6 ). Catalysis and electron flow are indicated by arrows. The possible PMF-driven reverse electron flow of Sdh2 is not shown, for clarity. Abbreviations: Mqo, malate:menaquinone oxidoreductase; Ndh, type II NADH:menaquinone oxidoreductase; Sdh2, succinate:menaquinone oxidoreductase 2; Nar, nitrate reductase; Cyd, cytochrome oxidase; Frd, FRD; Hyd, hydrogenase; MQ, menaquinone; A, unidentified electron acceptor. doi:10.1128/microbiolspec.MGM2-0015-2013.f3

Source: microbiolspec June 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0015-2013
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TABLE 1

Electron transport chain components and energy-generating machinery of mycobacteria

Source: microbiolspec June 2014 vol. 2 no. 3 doi:10.1128/microbiolspec.MGM2-0015-2013

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