title: Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite.
abstract: Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria.
authors.affiliation: Parasitology Unit, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Sanketha
authors.initials: S
authors.lastname: Kenthirapalan
authors.affiliation: Wellcome Trust Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Waters
authors.affiliation: Parasitology Unit, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.|Institute of Biology, Humboldt University, 10117 Berlin, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Matuschewski
authors.affiliation: Parasitology Unit, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.|Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.|Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Taco W A
authors.initials: TW
authors.lastname: Kooij
mesh_terms: D000818:Animals; D000852:Anopheles; D005260:Female; D008018:Life Cycle Stages; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000235:genetics / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins