Smyrnakou, X. | bioRxiv Science

bioRxiv2021

Phosphorylation of myosin A regulates Plasmodium sporozoite motility and is essential for efficient malaria transmission

Malaria-causing parasites rely on an actin-myosin based motor for the invasion of different host cells as well as tissue traversal in mosquitoes and vertebrates. The unusual myosin A of Plasmodium spp. has a unique N-terminal extension which is important for red blood cell invasion by P. falciparum merozoites in vitro and harbors a phosphorylation site at serine 19. Here, using the rodent-infecting P. berghei we show that serine 19 is essential for efficient transmission of Plasmodium by mosquitoes as S19A mutants show defects in mosquito salivary gland entry and migration of salivary gland sporozoites in both 2D and 3D environments. Our data suggests that entry into salivary glands represents the strongest barrier in parasite transmission and hence is the key determinant for evolution of the motility and invasion machinery of these parasites. HighlightsThe unusual N-terminal extension of Plasmodium myosin A is important for efficient gliding motility Altering the kinetics of the myosin A power stroke impacts Plasmodium life cycle progression and sporozoite motility Myosin A phosphorylation at serine 19 is important for malaria transmission by mosquitoes Salivary gland invasion emerges as key selection step for evolution of the parasite motor

molecular biology↗

bioRxiv2020

Malaria parasites differentially sense environmental elasticity during transmission

Transmission of malaria-causing parasites to and by the mosquito rely on active parasite migration and constitute bottlenecks in the Plasmodium life cycle. Parasite adaption to the biochemically and physically different environments must hence be a key evolutionary driver for transmission efficiency. To probe how subtle but physiologically relevant changes in environmental elasticity impact parasite migration, we introduce 2D and 3D polyacrylamide gels to study ookinetes, the parasite forms emigrating from the mosquito blood meal and sporozoites, the forms transmitted to the vertebrate host. We show that ookinetes adapt their migratory path but not their speed to environmental elasticity and are motile for over 24 hours on soft substrates. In contrast, sporozoites evolved more short-lived rapid gliding motility for rapidly crossing the skin. Strikingly, sporozoites are highly sensitive to substrate elasticity possibly to avoid adhesion on soft endothelial cells on their long way to the liver. Hence the two migratory stages of Plasmodium evolved different strategies to overcome the physical challenges posed by the respective environments and barriers they encounter. HighlightsPlasmodium ookinetes can move for over 24 hours on very soft substrates mimicking the blood meal Plasmodium ookinetes change their migration path according to substrate stiffness Plasmodium sporozoites are highly sensitive to subtle changes in substrate elasticity Sporozoite may have evolved to not attach to the soft endothelium to help reach the liver

biophysics↗