Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence

Abstract

Abstract: Toxoplasma gondii is a single-celled parasitic eukaryote that evolved to successfully propagate in any nucleated cell. As with any other eukaryote, its life cycle is regulated by signaling pathways controlled by kinases and phosphatases. T. gondii encodes an atypical bacterial-like phosphatase absent from mammalian genomes, named Shelph, after its first identification in the psychrophilic bacterium Schewanella sp. Here, we demonstrate that Toxoplasma Shelph is an active phosphatase localized in the parasite endoplasmic reticulum. The phenotyping of a shelph knockout (KO) line showed a minor impairment in invasion on human fibroblasts, while the other steps of the parasite lytic cycle were not affected. In contrast with Plasmodium ortholog Shelph1, this invasion deficiency was not correlated with any default in the biogenesis of secretory organelles. However, Shelph-KO parasites displayed a much-pronounced defect in virulence in vivo. These phenotypes could be rescued by genetic complementation, thus supporting an important function for Shelph in the context of a natural infection.