title: Plasmodium yoelii vitamin B5 pantothenate transporter candidate is essential for parasite transmission to the mosquito.
abstract: In nearly all non-photosynthetic cells, pantothenate (vitamin B5) transport and utilization are prerequisites for the synthesis of the universal essential cofactor Coenzyme A (CoA). Early studies showed that human malaria parasites rely on the uptake of pantothenate across the parasite plasma membrane for survival within erythrocytes. Recently, a P. falciparum candidate pantothenate transporter (PAT) was characterized by functional complementation in yeast. These studies revealed that PfPAT mediated survival of yeast cells in low pantothenate concentrations and restored sensitivity of yeast cells lacking pantothenate uptake to fenpropimorph. In addition, PfPAT was refractory to deletion in P. falciparum in vitro, but nothing is known about the in vivo functions of PAT in Plasmodium life cycle stages. Herein, we used gene-targeting techniques to delete PAT in Plasmodium yoelii. Parasites lacking PAT displayed normal asexual and sexual blood stage development compared to wild-type (WT) and WT-like p230p(-) parasites. However, progression from the ookinete to the oocyst stage and sporozoite formation were completely abolished in pat(-) parasites. These studies provide the first evidence for an essential role of a candidate pantothenate transport in malaria transmission to Anopheles mosquitoes. This will set the stage for the development of PAT inhibitors against multiple parasite life cycle stages.
authors.affiliation: 1] Tulane University, Department of Tropical Medicine, New Orleans, LA 70112, USA [2].
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hart
authors.affiliation: 1] Tulane University, Department of Tropical Medicine, New Orleans, LA 70112, USA [2].
authors.forename: Lauren
authors.initials: L
authors.lastname: Lawres
authors.affiliation: Tulane University, Department of Tropical Medicine, New Orleans, LA 70112, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Fritzen
authors.affiliation: Yale University School of Medicine, Section of Infectious Diseases, New Haven, CT 06520, USA.
authors.forename: Choukri
authors.initials: C
authors.lastname: Ben Mamoun
authors.affiliation: Tulane University, Department of Tropical Medicine, New Orleans, LA 70112, USA.
authors.forename: Ahmed S I
authors.initials: AS
authors.lastname: Aly
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D009033:Culicidae / Q000469:parasitology*; D008018:Life Cycle Stages / Q000502:physiology; D008288:Malaria / Q000469:parasitology / Q000635:transmission*; D033661:Oocysts / Q000378:metabolism; D010205:Pantothenic Acid / Q000378:metabolism*; D010271:Parasites / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism; D010967:Plasmodium yoelii / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism; D034101:Sporozoites / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D027981:Symporters; C119982:pantothenate transporter; D010205:Pantothenic Acid