A P lasmodium α/β‐hydrolase modulates the development of invasive stages

Summary 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 P lasmodium   BEM 46‐like protein ( PBLP ) and characterized it throughout the life cycle of the rodent malaria parasite P lasmodium yoelii. The P lasmodium   BEM 46‐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 (Δ pblp ) parasite lines showed that PBLP has an important role in erythrocytic stage merozoite development with Δ pblp parasites forming fewer merozoites during schizogony, which results in decreased parasitemia when compared with wild‐type ( WT ) parasites. Δ pblp 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 Δ pblp sporozoites showed no apparent defect in mosquito salivary gland infection, they showed decreased infectivity in hepatocytes in vitro . Similarly, mice infected with Δ pblp 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.