Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence

Scott A. Chisholm, Emma McHugh, Rachel Lundie, Matthew W A Dixon, Sreejoyee Ghosh, Meredith O'Keefe, Leann Tilley, Ming Kalanon, Tania F de Koning-Ward

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16 Citations (Scopus)

Abstract

Pathogenesis of malaria infections is linked to remodeling of erythrocytes, a process dependent on the trafficking of hundreds of parasite-derived proteins into the host erythrocyte. Recent studies have demonstrated that the Plasmodium translocon of exported proteins (PTEX) serves as the central gateway for trafficking of these proteins, as inducible knockdown of the core PTEX constituents blocked the trafficking of all classes of cargo into the erythrocyte. However, the role of the auxiliary component PTEX88 in protein export remains less clear. Here we have used inducible knockdown technologies in P. falciparum and P. berghei to assess the role of PTEX88 in parasite development and protein export, which reveal that the in vivo growth of PTEX88-deficient parasites is hindered. Interestingly, we were unable to link this observation to a general defect in export of a variety of known parasite proteins, suggesting that PTEX88 functions in a different fashion to the core PTEX components. Strikingly, PTEX88-deficient P. berghei were incapable of causing cerebral malaria despite a robust pro-inflammatory response from the host. These parasites also exhibited a reduced ability to sequester in peripheral tissues and were removed more readily from the circulation by the spleen. In keeping with these findings, PTEX88-deficient P. falciparum-infected erythrocytes displayed reduced binding to the endothelial cell receptor, CD36. This suggests that PTEX88 likely plays a specific direct or indirect role in mediating parasite sequestration rather than making a universal contribution to the trafficking of all exported proteins.

Original languageEnglish
Article numbere0149296
Number of pages21
JournalPLoS ONE
Volume11
Issue number2
DOIs
Publication statusPublished - 17 Feb 2016
Externally publishedYes

Keywords

  • parasitic diseases
  • plasmodium
  • malarial parasites
  • red blood cells
  • spleen
  • parasitic cell cycles
  • parasitemia
  • parasitic life cycles

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