The exported chaperone PfHsp70x is dispensable for the Plasmodium falciparum intraerythrocytic life cycle

David W. Cobb, Anat Florentin, Manuel A. Fierro, Michelle Krakowiak, Julie M. Moore, Vasant Muralidharan

Research output: Contribution to journalArticlepeer-review

Abstract

Export of parasite proteins into the host erythrocyte is essential for survival of Plasmodium falciparum during its asexual life cycle. 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 cochaperones, 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, P. falciparum Hsp70x (PfHsp70x), is exported with them. PfHsp70x is absent in most Plasmodium species and is found only in P. falciparum and closely related species that infect apes. Herein, we have utilized clustered regularly interspaced short palindromic repeat (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 dihydrofolate reductase (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 life cycle. The effect of PfHsp70x knockdown/ knockout on the export of proteins to the host red blood cell (RBC), including the critical virulence factor P. falciparum erythrocyte membrane protein 1 (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.

Original languageAmerican English
Article numbere00363-17
JournalmSphere
Volume2
Issue number5
DOIs
StatePublished - 1 Sep 2017
Externally publishedYes

Keywords

  • Hsp70
  • Malaria
  • Plasmodium falciparum
  • Protein export

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

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