Houze, S. | Search bioRxiv

bioRxiv2020

Plasmodium falciparum sexual parasites regulate infected erythrocyte permeability

To ensure the transport of nutrients necessary for their survival, Plasmodium falciparum parasites increase erythrocyte permeability to diverse solutes. These New Permeation Pathways (NPP) have been extensively characterized in the pathogenic asexual parasite stages, however the existence of NPP has never been investigated in gametocytes, the sexual stages responsible for transmission to mosquitoes. Here, we show that NPP are still active in erythrocytes infected with immature gametocytes and that this activity declines along gametocyte maturation. Our results indicate that NPP are regulated by cyclic AMP (cAMP) signaling cascade during sexual parasite stages, and that the decrease in cAMP levels in mature stages results in a slowdown of NPP activity. We also show that NPP facilitate the uptake of artemisinin derivatives and that phosphodiesterase (PDE) inhibitors can reactivate NPP and increase drug uptake in mature gametocyte-infected erythrocytes. These processes are predicted to play a key role in P. falciparum gametocyte biology and susceptibility to antimalarials.

microbiology↗

bioRxiv2020

Population genomic evidence of a Southeast Asian origin of Plasmodium vivax

Plasmodium vivax is the most prevalent and widespread human malaria parasite, with almost three billion people living at risk of infection. With the discovery of its closest genetic relatives in African great apes (Plasmodium vivax-like), the origin of P. vivax has been proposed to be located in the sub-Saharan African area. However, the limited number of genetic markers and samples investigated questioned the robustness of this result. Here, we examined the population genomic variation of 447 human P. vivax strains and 19 ape P. vivax-like strains originating from 24 different countries across the world. We identified 2,005,455 high quality single-nucleotide polymorphism loci allowing us to conduct an extensive characterization to date of P. vivax worldwide genetic variation. Phylogenetic relationships between human and ape Plasmodium revealed that P. vivax is a sister clade of P. vivax-like, not included within the radiation of P. vivax-like. By investigating a variety of aspects of P. vivax variation, we identified several striking geographical patterns in summary statistics as function of increasing geographic distance from Southeast Asia, suggesting that P. vivax may derived from serial founder effects from a single origin located in Asia.

evolutionary biology↗