Disruption of Plasmodium Sporozoite Transmission by Depletion of Sporozoite Invasion-Associated Protein 1

Accumulation of infectious Plasmodium sporozoites in Anopheles spp. salivary glands marks the final step of the complex development of the malaria parasite in the insect vector. Sporozoites are formed inside midgut-associated oocysts and actively egress into the mosquito hemocoel. Traversal of the salivary gland acinar cells correlates with the sporozoite's capacity to perform continuous gliding motility. Here, we characterized the cellular role of the Plasmodium berghei sporozoite invasion-associated protein 1 (SIAP-1). Intriguingly, SIAP-1 orthologs are found exclusively in apicomplexan hemoprotozoa, parasites that are transmitted by arthropod vectors, e.g., Plasmodium, Babesia, and Theileria species. By fluorescent tagging with mCherry, we show that SIAP-1 is expressed in oocyst-derived and salivary gland-associated sporozoites, where it accumulates at the apical tip. Targeted disruption of SIAP-1 does not affect sporozoite formation but causes a partial defect in sporozoite egress from oocysts and abolishes sporozoite colonization of mosquito salivary glands. Parasites with the siap-1(-) mutation are blocked in their capacity to perform continuous gliding motility. We propose that arthropod-transmitted apicomplexan parasites specifically express secretory factors, such as SIAP-1, that mediate efficient oocyst exit and migration to the salivary glands.