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

Abstract

AbstractMalaria-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 motilityAltering the kinetics of the myosin A power stroke impacts Plasmodium life cycle progression and sporozoite motilityMyosin A phosphorylation at serine 19 is important for malaria transmission by mosquitoesSalivary gland invasion emerges as key selection step for evolution of the parasite motor