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Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis

Author

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  • Robert S. Jansen

    (Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College)

  • Lungelo Mandyoli

    (Department of Biochemistry and Biophysics, Texas A&M University)

  • Ryan Hughes

    (Department of Biochemistry and Biophysics, Texas A&M University)

  • Shoko Wakabayashi

    (Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health)

  • Jessica T. Pinkham

    (Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health)

  • Bruna Selbach

    (Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College)

  • Kristine M. Guinn

    (Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health)

  • Eric J. Rubin

    (Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health)

  • James C. Sacchettini

    (Department of Biochemistry and Biophysics, Texas A&M University)

  • Kyu Y. Rhee

    (Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College
    Department of Microbiology & Immunology, Weill Cornell Medical College)

Abstract

Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis, and mediates an essential but underrecognized role in metabolism: nitrogen distribution. Rv3722c deficiency leads to virulence attenuation in macrophages and mice. Our results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets in M. tuberculosis.

Suggested Citation

  • Robert S. Jansen & Lungelo Mandyoli & Ryan Hughes & Shoko Wakabayashi & Jessica T. Pinkham & Bruna Selbach & Kristine M. Guinn & Eric J. Rubin & James C. Sacchettini & Kyu Y. Rhee, 2020. "Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15876-8
    DOI: 10.1038/s41467-020-15876-8
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    Cited by:

    1. Niek F. de Jonge & Joris J. R. Louwen & Elena Chekmeneva & Stephane Camuzeaux & Femke J. Vermeir & Robert S. Jansen & Florian Huber & Justin J. J. van der Hooft, 2023. "MS2Query: reliable and scalable MS2 mass spectra-based analogue search," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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