title: A Plasmodium α/β-hydrolase modulates the development of invasive stages.
abstract: The bud emergence (BEM)46 proteins are evolutionarily conserved members of the α/β-hydrolase superfamily, which includes enzymes with diverse functions and a wide range of substrates. Here, we identified a Plasmodium BEM46-like protein (PBLP) and characterized it throughout the life cycle of the rodent malaria parasite Plasmodium yoelii. The Plasmodium BEM46-like protein is shown to be closely associated with the parasite plasma membrane of asexual erythrocytic stage schizonts and exo-erythrocytic schizonts; however, PBLP localizes to unique intracellular structures in sporozoites. Generation and analysis of P. yoelii knockout (Δpblp) parasite lines showed that PBLP has an important role in erythrocytic stage merozoite development with Δpblp parasites forming fewer merozoites during schizogony, which results in decreased parasitemia when compared with wild-type (WT) parasites. Δpblp parasites showed no defects in gametogenesis or transmission to mosquitoes; however, because they formed fewer oocysts there was a reduction in the number of developed sporozoites in infected mosquitoes when compared with WT. Although Δpblp sporozoites showed no apparent defect in mosquito salivary gland infection, they showed decreased infectivity in hepatocytes in vitro. Similarly, mice infected with Δpblp sporozoites exhibited a delay in the onset of blood-stage patency, which is likely caused by reduced sporozoite infectivity and a discernible delay in exo-erythrocytic merozoite formation. These data are consistent with the model that PBLP has an important role in parasite invasive-stage morphogenesis throughout the parasite life cycle.
authors.affiliation: Center for Infectious Disease Research, formerly Seattle BioMedical Research Institute, Seattle, WA, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Groat-Carmona
authors.affiliation: Center for Infectious Disease Research, formerly Seattle BioMedical Research Institute, Seattle, WA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Kain
authors.affiliation: Center for Infectious Disease Research, formerly Seattle BioMedical Research Institute, Seattle, WA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Brownell
authors.affiliation: Center for Infectious Disease Research, formerly Seattle BioMedical Research Institute, Seattle, WA, USA.
authors.forename: Alyse N
authors.initials: AN
authors.lastname: Douglass
authors.affiliation: School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
authors.forename: Ahmed S I
authors.initials: AS
authors.lastname: Aly
authors.affiliation: Center for Infectious Disease Research, formerly Seattle BioMedical Research Institute, Seattle, WA, USA.|Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D009033:Culicidae; D017353:Gene Deletion; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D052940:Merozoites / Q000201:enzymology / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010967:Plasmodium yoelii / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D034101:Sporozoites / Q000201:enzymology / Q000254:growth & development
chemical_list: D008565:Membrane Proteins; D006867:Hydrolases