title: The Plasmodium protein P113 supports efficient sporozoite to liver stage conversion in vivo.
abstract: Invasive stages of Plasmodium parasites possess distinct integral and peripheral membrane proteins that mediate host cell attachment and invasion. P113 is an abundant protein in detergent-resistant high molecular weight complexes in Plasmodium schizonts, but is unusual since expression extends to gametocytes and sporozoites. In this study, we tested whether P113 performs important functions for parasite propagation in Plasmodium berghei. We show that pre-erythrocytic expression of P113 displays key signatures of upregulated in infectious sporozoites (UIS) genes, including control by the liver stage master regulator SLARP. Targeted gene deletion resulted in viable blood stage parasites that displayed no signs of blood stage growth defects. p113(-) parasites propagated normally through the life cycle until mature sporozoites, but displayed defects during natural sporozoite transmission, leading to a delay to patency in infected animals. By comparative in vitro and in vivo analysis of pre-erythrocytic development and using a xeno-diagnostic test we show that ablation of P113 results in lower sporozoite to liver stage conversion and, as a consequence, reduced merozoite output in vivo, without delaying liver stage development. We conclude that p113 is dispensable for Plasmodium life cycle progression and plays auxiliary roles during pre-erythrocytic development.
authors.affiliation: Max Planck Institute for Infection Biology, Parasitology Unit, 10117 Berlin, Germany. Electronic address: offeddu@mpiib-berlin.mpg.de.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Offeddu
authors.affiliation: Max Planck Institute for Infection Biology, Parasitology Unit, 10117 Berlin, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rauch
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013 Paris, France; INSERM U1135, CIMI-Paris, 75013 Paris, France; CNRS ERL 8255, CIMI-Paris, 75013 Paris, France. Electronic address: olivier.silvie@inserm.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Silvie
authors.affiliation: Max Planck Institute for Infection Biology, Parasitology Unit, 10117 Berlin, Germany; Institute of Biology, Humboldt University, 10117 Berlin, Germany. Electronic address: matuschewski@mpiib-berlin.mpg.de.
authors.forename: Kai
authors.initials: K
authors.lastname: Matuschewski
mesh_terms: D000818:Animals; D009033:Culicidae / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006790:Host-Parasite Interactions; D008018:Life Cycle Stages; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology / Q000635:transmission; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010962:Plasmodium berghei / Q000166:cytology / Q000254:growth & development / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D034101:Sporozoites / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins
keywords: Apicomplexa; Experimental genetics; Liver stage; Malaria; P113; Plasmodium berghei