title: Perforin-like protein PPLP4 is crucial for mosquito midgut infection by Plasmodium falciparum.
abstract: The genomes of Plasmodium parasites encode for five perforin-like proteins, PPLP1-5, and four of them have previously been demonstrated to be involved in disruption of host cell barriers. We now show that the fifth perforin, PPLP4, is crucial for infection of the mosquito vector by Plasmodium falciparum parasites. PPLP4 is expressed in the blood and mosquito midgut stages in granular structures. In gametocytes, PPLP4 expression is specific to the female gender, while ookinetes show a PPLP4 localization at the apical pole. Gene disruption of pplp4 results in no phenotypical change during blood stage replication, gametocyte development or gametogenesis, while mosquitoes fed with PPLP4-deficient gametocytes display a severe reduction in oocyst numbers, and an accumulation of ookinetes in the mosquito midguts was observed. In conclusion, we propose an essential role for PPLP4 in infection of the mosquito midgut, presumably by mediating ookinete traversal through the midgut epithelium.
authors.affiliation: Cellular and Applied Infection Biology Section, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Wirth
authors.affiliation: Cellular and Applied Infection Biology Section, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bennink
authors.affiliation: Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Str. 2/D15, 97080 Würzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheuermayer
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstr. 6, 52074 Aachen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Cellular and Applied Infection Biology Section, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstr. 6, 52074 Aachen, Germany. Electronic address: gabriele.pradel@molbiotech.rwth-aachen.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pradel
mesh_terms: D000818:Animals; D009033:Culicidae / Q000469:parasitology*; D041981:Gastrointestinal Tract / Q000469:parasitology; D010963:Plasmodium falciparum / Q000254:growth & development*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D052899:Pore Forming Cytotoxic Proteins; D015800:Protozoan Proteins
keywords: Gametocyte; Malaria; Mosquito; Ookinete; Perforin-like protein; Plasmodium falciparum; Transmission