Bottoms up! Malaria parasite invasion the right way around

The recent demonstration of Plasmodium spp. merozoite gliding motility changes our understanding of how the merozoite actively seeks out and potentially selects a red blood cell (RBC) to invade.The observation that motility and RBC invasion is in the direction of the merozoite’s wider end will require significant changes in how merozoite invasion is represented and potentially our understanding of the biophysics of invasion compared to the current standard egg-shaped merozoite invasion model.Flipping the model to one where the wider end of the merozoite is the apex supports representing merozoites packed into a mature schizont in a wedge-shaped pattern with the wider apical end facing out (evidenced by many electron, expansion, and immunofluorescence microscopy images), instead of the egg-shaped merozoite model where the wider end is closer to the centre. A critical part of the malaria parasite’s life cycle is invasion of red blood cells (RBCs) by merozoites. Inside RBCs, the parasite forms a schizont, which undergoes segmentation to produce daughter merozoites. These cells are released, establishing cycles of invasion. Traditionally, merozoites are represented as nonmotile, egg-shaped cells that invade RBCs ‘narrower end’ first and pack within schizonts with this narrower end facing outwards. Here, we discuss recent evidence and re-evaluate previous data which suggest that merozoites are capable of motility and have spherical or elongated-teardrop shapes. Furthermore, merozoites invade RBCs ‘wider end’ first and pack within schizonts with this wider end facing outwards. We encourage the field to review this revised model and consider its implications for future studies. A critical part of the malaria parasite’s life cycle is invasion of red blood cells (RBCs) by merozoites. Inside RBCs, the parasite forms a schizont, which undergoes segmentation to produce daughter merozoites. These cells are released, establishing cycles of invasion. Traditionally, merozoites are represented as nonmotile, egg-shaped cells that invade RBCs ‘narrower end’ first and pack within schizonts with this narrower end facing outwards. Here, we discuss recent evidence and re-evaluate previous data which suggest that merozoites are capable of motility and have spherical or elongated-teardrop shapes. Furthermore, merozoites invade RBCs ‘wider end’ first and pack within schizonts with this wider end facing outwards. We encourage the field to review this revised model and consider its i