Reticulon and REEP family of proteins stabilize the high curvature of endoplasmic reticulum (ER) tubules. P. berghei Yop1 (Pb Yop1) is a REEP5 homolog in Plasmodium . Here we characterize its function using a gene‐knockout (Pb yop1∆). Pb yop1∆ asexual stage parasites display abnormal ER architecture and an enlarged digestive vacuole. The erythrocytic cycle of Pb yop1∆ parasites is severely attenuated and the incidence of experimental cerebral malaria is significantly decreased in Pb yop1∆‐infected mice.
Morphogenesis of many protozoans depends on a polarized establishment of cytoskeletal structures. In malaria‐causing parasites, this can be observed when a round zygote develops into an elongated motile ookinete within the mosquito stomach. This morphogenesis is mediated by the pellicle cytoskeletal structures, including the inner membrane complex (IMC) and the underlying subpellicular microtubules (SPMs).
Plasmodium parasites that cause malaria produce plasmepsins (PMs), pepsin‐like aspartic proteases that are important antimalarial drug targets due to their role in host hemoglobin degradation. The enzymes are synthesized as inactive zymogens (pro‐PMs) and the mechanism of their conversion to the active, mature forms has not been clearly elucidated. Our structural investigations of vacuolar pro‐PMs with truncated prosegment (pro‐tPMs) reveal that the formation of the S‐shaped dimer is their innate property. Further structural studies, biochemical analysis, and molecular dynamics simulations indicate that disruption of the Tyr‐Asp loop (121p‐4), coordinated with the movement of the loop L1 (237‐247) and helix H2 (101p‐113p) are responsible for the extension of the pro‐mature region (harboring the cleavage site).
Endocytosis is critical for many functions in eukaryotic cells. Uptake of host cell cytosol, an indispensable endocytic process in malaria blood-stage parasites, has been known for a long time. However, it is only recently that the proteins involved in this process have started to emerge.
Avian malaria is a mosquito-borne disease caused by Plasmodium spp. protozoa. Although these parasites have been extensively studied in North America and Eurasia, knowledge on the diversity of Plasmodium, its vectors and avian hosts in Africa is scarce. In this study, we report on natural malarial infections in free-ranging sparrows (Passer domesticus) sampled at Giza Governorate, Egypt. Parasites were morphologically characterized as Plasmodium cathemerium based on the examination of thin blood smears from the avian host.
The Nigerian Government is scaling up the distribution of insecticide-treated bed nets for malaria control, but the lack of surveillance data, especially in the Sudan/Sahel region of the country, may hinder targeting priority populations. Here, the vectorial role and insecticide resistance profile of a population of a major malaria vector Anopheles funestus sensu stricto from Sahel of Nigeria was characterised.
Malaria, caused by the protozoan parasite Plasmodium and transmitted by Anopheles mosquitoes, represents a major threat to human health. Plasmodium’s infection cycle in the Anopheles vector is critical for transmission of the parasite between humans. The midgut-stage bottleneck of infection is largely imposed by the mosquito’s innate immune system. microRNAs (miRNAs, small noncoding RNAs that bind to target RNAs to regulate gene expression) are also involved in regulating immunity and the anti-Plasmodium defense in mosquitoes.
The rapid evolution of resistance in the malaria parasite to every single drug developed against it calls for the urgent identification of new molecular targets. Using a stain specific for the detection of intracellular amyloid deposits in live cells we have detected the presence of abundant protein aggregates in Plasmodium falciparum blood stages and female gametes cultured in vitro, in the blood stages of mice infected by Plasmodium yoelii, and in the mosquito stages of the murine malaria species Plasmodium berghei.
MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics and antimalarial activity of a tablet formulation of MMV390048.
MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model.