Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver-stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.
Graphical Abstract
Highlights • A library of Plasmodium falciparum sporozoite membrane and secreted proteins. • Systematic extracellular interaction screening identifies novel protein complexes. • Interactions are conserved across Plasmodium species. • Essential role for genes encoding p24 complex proteins in liver-stage infection.
In Brief Malaria remains one of the world's most deadly infectious diseases, and host infection is initiated when the sporozoite form of the P. falciparum parasite is transmitted by the bite of an infected mosquito. Here, we compile a library of soluble recombinant sporozoite cell surface and secreted proteins and test them for direct interactions using an extracellular protein interaction assay. We identify three conserved complexes and show that one, the p24 complex, is essential for host liver-stage infection.