Functional characterization of Plasmodium ETRAMP proteins in the liver stage

HILMER, CECILIE; MATUSCHEWSKI, KAI; BRANDSMA, ARIANNE; MONTAGNA, GEORGINA NURI

Hamburgo

Simposio; 14th Malaria Meeting; 2019

Bernhard Nocht Institute for Tropical Medicine

Early transcribed membrane proteins (ETRAMPs) are unique to malaria parasites. Upregulated in infectious sporozoites 4 (UIS4) is essential for P. berghei as uis4 deletion arrests parasite at liver stage. In order to characterize UIS4 functional domains, we generated P. berghei parasites carrying a C-terminally truncated version of UIS4. We observed uis4Δc parasites are severely impaired in liver stage development indicating an important role of the C-terminal domain for UIS4 function. Thus far, we observed an intact parasitophorous vacuole membrane (PVM) structure in these parasites suggesting that this ETRAMP is dispensable for PVM structuring. Preliminary data indicate P. falciparum ETRAMP8 as the best candidate to complement UIS4 function. To test this hypothesis, we generated transgenic P. berghei parasites where UIS4 was replaced by ETRAMP8. We detected that ETRAMP8 is expressed at mRNA level in uis4::ETRAMP8 complementation parasites however liver stage development of uis4::ETRAMP8 was impaired in vitro, indicating that ETRAMP8 failed to substitute UIS4 function in vivo. These results suggest that Plasmodium parasites express tailor-made PVM proteins that might, at least, partially explain the narrow host range of malaria parasites.