The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron sulfur cluster assembly and tRNA modification

  1. Russell P Swift
  2. Rubayet Elahi
  3. Krithika Rajaram
  4. Hans B Liu
  5. Sean T Prigge  Is a corresponding author
  1. Johns Hopkins University, United States

Abstract

Iron sulfur clusters (FeS) are ancient and ubiquitous protein cofactors that play fundamental roles in many aspects of cell biology. These cofactors cannot be scavenged or trafficked within a cell and thus must be synthesized in any subcellular compartment where they are required. We examined the FeS synthesis proteins found in the relict plastid organelle, called the apicoplast, of the human malaria parasite Plasmodium falciparum. Using a chemical bypass method, we deleted four of the FeS pathway proteins involved in sulfur acquisition and cluster assembly and demonstrated that they are all essential for parasite survival. However, the effect that these deletions had on the apicoplast organelle differed. Deletion of the cysteine desulfurase SufS led to disruption of the apicoplast organelle and loss of the organellar genome, whereas the other deletions did not affect organelle maintenance. Ultimately, we discovered that the requirement of SufS for organelle maintenance is not driven by its role in FeS biosynthesis, but rather, by its function in generating sulfur for use by MnmA, a tRNA modifying enzyme that we localized to the apicoplast. Complementation of MnmA and SufS activity with a bacterial MnmA and its cognate cysteine desulfurase, strongly suggests that the parasite SufS provides sulfur for both FeS biosynthesis and tRNA modification in the apicoplast. The dual role of parasite SufS is likely to be found in other plastid-containing organisms and highlights the central role of this enzyme in plastid biology.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1, 2, 3, 4, 5, 6, 7.

Article and author information

Author details

  1. Russell P Swift

    Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Rubayet Elahi

    Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1561-5257
  3. Krithika Rajaram

    Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4830-5471
  4. Hans B Liu

    Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sean T Prigge

    Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States
    For correspondence
    sprigge2@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9684-1733

Funding

Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health (Postdoctoral fellowship)

  • Rubayet Elahi

National Institute of Allergy and Infectious Diseases (R01AI125534)

  • Sean T Prigge

National Institute of Allergy and Infectious Diseases (R21AI101589)

  • Sean T Prigge

National Institute of Allergy and Infectious Diseases (T32AI007417)

  • Krithika Rajaram

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Swift et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Russell P Swift
  2. Rubayet Elahi
  3. Krithika Rajaram
  4. Hans B Liu
  5. Sean T Prigge
(2023)
The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron sulfur cluster assembly and tRNA modification
eLife 12:e84491.
https://doi.org/10.7554/eLife.84491

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https://doi.org/10.7554/eLife.84491