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The exported chaperone PfHsp70x is dispensable for the Plasmodium falciparum intraerythrocytic lifecycle

David W. Cobb, Anat Florentin, Manuel A. Fierro, Michelle Krakowiak, Julie M. Moore, View ORCID ProfileVasant Muralidharan
doi: https://doi.org/10.1101/113365
David W. Cobb
1Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America
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Anat Florentin
1Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America
2Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, United States of America
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Manuel A. Fierro
1Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America
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Michelle Krakowiak
1Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America
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Julie M. Moore
2Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, United States of America
3Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America
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Vasant Muralidharan
1Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America
2Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, United States of America
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  • ORCID record for Vasant Muralidharan
  • For correspondence: vasant@uga.edu
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Abstract

Export of parasite proteins into the host erythrocyte is essential for survival of Plasmodium falciparum during its asexual lifecycle. While several studies described key factors within the parasite that are involved in protein export, the mechanisms employed to traffic exported proteins within the host cell are currently unknown. Members of the Hsp70 family of chaperones, together with their Hsp40 co-chaperones, facilitate protein trafficking in other organisms, and are thus likely used by P. falciparum in the trafficking of its exported proteins. A large group of Hsp40 proteins is encoded by the parasite and exported to the host cell, but only one Hsp70, PfHsp70x, is exported with them.

PfHsp70x is absent from most Plasmodium species and is found only in P. falciparum and closely-related species that infect Apes. Herein, we have utilized CRISPR/Cas9 genome editing in P. falciparum to investigate the essentiality of PfHsp70x. We show that parasitic growth was unaffected by knockdown of PfHsp70x using both the DHFR-based Destabilization Domain and the glmS ribozyme system. Similarly, a complete gene knockout of PfHsp70x did not affect the ability of P. falciparum to proceed through its intraerythrocytic lifecycle. The effect of PfHsp70x knockdown/knockout on the export of proteins to the host RBC, including the critical virulence factor PfEMP1, was tested and we found that this process was unaffected. These data show that although PfHsp70x is the sole exported Hsp70, it is not essential for the asexual development of P. falciparum.

Importance Half of the world’s population lives at risk for malaria. The intraerythrocytic lifecycle of Plasmodium spp. is responsible for clinical manifestations of malaria; therefore, knowledge of the parasite’s ability to survive within the erythrocyte is needed to combat the deadliest agent of malaria, P. falciparum. An outstanding question in the field is how P. falciparum undertakes the essential process of trafficking its proteins within the host cell. In most organisms, chaperones such as Hsp70 are employed in protein trafficking. Of the human-disease causing Plasmodium species, the chaperone PfHsp70x is unique to P. falciparum, and it is the only parasite protein of its kind exported to the host (1). This has placed PfHsp70x as an ideal target to inhibit protein trafficking and kill the parasite. However, we show that PfHsp70x is not required for export of parasite effectors nor is it essential for parasite survival inside of the RBC.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 11, 2017.
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The exported chaperone PfHsp70x is dispensable for the Plasmodium falciparum intraerythrocytic lifecycle
David W. Cobb, Anat Florentin, Manuel A. Fierro, Michelle Krakowiak, Julie M. Moore, Vasant Muralidharan
bioRxiv 113365; doi: https://doi.org/10.1101/113365
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The exported chaperone PfHsp70x is dispensable for the Plasmodium falciparum intraerythrocytic lifecycle
David W. Cobb, Anat Florentin, Manuel A. Fierro, Michelle Krakowiak, Julie M. Moore, Vasant Muralidharan
bioRxiv 113365; doi: https://doi.org/10.1101/113365

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