Structural basis for chirality and directional motility of P lasmodium sporozoites

Summary P lasmodium sporozoites can move at high speed for several tens of minutes, which is essential for the initial stage of a malaria infection. The crescent‐shaped sporozoites move on 2 D substrates preferably in the same direction on circular paths giving raise to helical paths in 3 D matrices. Here we determined the structural basis that underlies this type of movement. Immature, non‐motile sporozoites were found to lack the subpellicular network required for obtaining the crescent parasite shape. In vitro , parasites moving in the favoured direction move faster and more persistent than the few parasites that move in the opposite direction. Photobleaching experiments showed that sporozoites flip their ventral side up when switching the direction of migration. Cryo‐electron tomography revealed a polarized arrangement of microtubules and polar rings towards the substrate in P lasmodium sporozoites, but not in the related parasite T oxoplasma gondii . As aconsequence, secretory vesicles, which release proteins involved in adhesion, migration and invasion at the front end of the parasite, are delivered towards the substrate. The resulting chiral structure of the parasite appears to determine the unique directionality of movement and could explain how the sporozoite achieves rapid and sustained directional motility in the absence of external stimuli.