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Epigenetic Phosphorylation Control of Infection and Persistence

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  • Authors: Melissa Richard-Greenblatt1, Yossef Av-Gay2
  • Editors: William R. Jacobs Jr.3, Helen McShane4, Valerie Mizrahi5, Ian M. Orme6
    Affiliations: 1: Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada; 2: Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada; 3: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 4: University of Oxford, Oxford OX3 7DQ, United Kingdom; 5: University of Cape Town, Rondebosch 7701, South Africa; 6: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0005-2015
  • Received 22 December 2015 Accepted 27 January 2017 Published 10 March 2017
  • Yossef Av-Gay, [email protected]
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  • Abstract:

    Reversible protein phosphorylation is the most common type of epigenetic posttranslational modification in living cells used as a major regulation mechanism of biological processes. The genome encodes for 11 serine/threonine protein kinases that are responsible for sensing environmental signals to coordinate a cellular response to ensure the pathogen’s infectivity, survival, and growth. To overcome killing mechanisms generated within the host during infection, enters a state of nonreplicating persistence that is characterized by arrested growth, limited metabolic activity, and phenotypic resistance to antimycobacterial drugs. In this article we focus our attention on the role of serine/threonine protein kinases in sensing the host environment to coordinate the bacilli’s physiology, including growth, cell wall components, and central metabolism, to establish a persistent infection.

  • Citation: Richard-Greenblatt M, Av-Gay Y. 2017. Epigenetic Phosphorylation Control of Infection and Persistence. Microbiol Spectrum 5(2):TBTB2-0005-2015. doi:10.1128/microbiolspec.TBTB2-0005-2015.


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Reversible protein phosphorylation is the most common type of epigenetic posttranslational modification in living cells used as a major regulation mechanism of biological processes. The genome encodes for 11 serine/threonine protein kinases that are responsible for sensing environmental signals to coordinate a cellular response to ensure the pathogen’s infectivity, survival, and growth. To overcome killing mechanisms generated within the host during infection, enters a state of nonreplicating persistence that is characterized by arrested growth, limited metabolic activity, and phenotypic resistance to antimycobacterial drugs. In this article we focus our attention on the role of serine/threonine protein kinases in sensing the host environment to coordinate the bacilli’s physiology, including growth, cell wall components, and central metabolism, to establish a persistent infection.

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Hierarchy of STPK activation in response to extracellular and intracellular signals. Master STPKs (blue) sense environmental signals and further cross-phosphorylate the kinase domains of signal transducing (purple) and substrate (red) STPKs to propagate signals and regulate specific downstream proteins. (Figure modified from reference 28 ).

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0005-2015
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STPK cell signaling network associated with persistence. STPKs sense specific environmental cues (starvation, hypoxia, and nitric oxide) and coordinate a physiological response that triggers to enter a state of nonreplicating persistence.

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0005-2015
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Biochemically verified substrates of serine/threonine protein kinases

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0005-2015
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Growth and persistence phenotypes of serine/threoneine protein kinase mutants

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0005-2015
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Effect of phosphorylation on serine/threonine protein kinase substrates

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TBTB2-0005-2015

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