Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence
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 phosphat...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-12-01
|
| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00350-22 |
| _version_ | 1798003870732910592 |
|---|---|
| author | Rania Najm Maguy Hamie Laurence Berry-Sterkers Maryse Lebrun Hiba El Hajj Mauld H. Lamarque |
| author_facet | Rania Najm Maguy Hamie Laurence Berry-Sterkers Maryse Lebrun Hiba El Hajj Mauld H. Lamarque |
| author_sort | Rania Najm |
| collection | DOAJ |
| description | 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. IMPORTANCE Toxoplasma gondii belongs to the Apicomplexa phylum, which comprises more than 5,000 species, among which is Plasmodium falciparum, the notorious agent of human malaria. Intriguingly, the Apicomplexa genomes encode at least one phosphatase closely related to the bacterial Schewanella phosphatase, or Shelph. To better understand the importance of these atypical bacterial enzymes in eukaryotic parasites, we undertook the functional characterization of T. gondii Shelph. Our results uncovered its subcellular localization and its enzymatic activity, revealed its subtle involvement during the tachyzoite invasion step of the lytic cycle, and more importantly, highlighted a critical requirement of this phosphatase for parasite propagation in mice. Overall, this study revealed an unexpected role for T. gondii Shelph in the maintenance of parasite virulence in vivo. |
| first_indexed | 2024-04-11T12:14:32Z |
| format | Article |
| id | doaj.art-fcc3c339335f47d8b3ad117f03336246 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-04-11T12:14:32Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-fcc3c339335f47d8b3ad117f033362462022-12-22T04:24:26ZengAmerican Society for MicrobiologymSphere2379-50422022-12-017610.1128/msphere.00350-22Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite VirulenceRania Najm0Maguy Hamie1Laurence Berry-Sterkers2Maryse Lebrun3Hiba El Hajj4Mauld H. Lamarque5Department of Biomedical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab EmiratesDepartment of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, LebanonLPHI, UMR 5235 CNRS, Université de Montpellier, Montpellier, FranceLPHI, UMR 5235 CNRS, Université de Montpellier, Montpellier, FranceDepartment of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, LebanonLPHI, UMR 5235 CNRS, Université de Montpellier, Montpellier, FranceABSTRACT 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. IMPORTANCE Toxoplasma gondii belongs to the Apicomplexa phylum, which comprises more than 5,000 species, among which is Plasmodium falciparum, the notorious agent of human malaria. Intriguingly, the Apicomplexa genomes encode at least one phosphatase closely related to the bacterial Schewanella phosphatase, or Shelph. To better understand the importance of these atypical bacterial enzymes in eukaryotic parasites, we undertook the functional characterization of T. gondii Shelph. Our results uncovered its subcellular localization and its enzymatic activity, revealed its subtle involvement during the tachyzoite invasion step of the lytic cycle, and more importantly, highlighted a critical requirement of this phosphatase for parasite propagation in mice. Overall, this study revealed an unexpected role for T. gondii Shelph in the maintenance of parasite virulence in vivo.https://journals.asm.org/doi/10.1128/msphere.00350-22Toxoplasma gondiienzyme kineticsinfectious diseaseparasitologyreverse genetic analysisserine/threonine phosphatases |
| spellingShingle | Rania Najm Maguy Hamie Laurence Berry-Sterkers Maryse Lebrun Hiba El Hajj Mauld H. Lamarque Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence mSphere Toxoplasma gondii enzyme kinetics infectious disease parasitology reverse genetic analysis serine/threonine phosphatases |
| title | Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence |
| title_full | Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence |
| title_fullStr | Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence |
| title_full_unstemmed | Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence |
| title_short | Toxoplasma Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence |
| title_sort | toxoplasma shelph a phosphatase located in the parasite endoplasmic reticulum is required for parasite virulence |
| topic | Toxoplasma gondii enzyme kinetics infectious disease parasitology reverse genetic analysis serine/threonine phosphatases |
| url | https://journals.asm.org/doi/10.1128/msphere.00350-22 |
| work_keys_str_mv | AT ranianajm toxoplasmashelphaphosphataselocatedintheparasiteendoplasmicreticulumisrequiredforparasitevirulence AT maguyhamie toxoplasmashelphaphosphataselocatedintheparasiteendoplasmicreticulumisrequiredforparasitevirulence AT laurenceberrysterkers toxoplasmashelphaphosphataselocatedintheparasiteendoplasmicreticulumisrequiredforparasitevirulence AT maryselebrun toxoplasmashelphaphosphataselocatedintheparasiteendoplasmicreticulumisrequiredforparasitevirulence AT hibaelhajj toxoplasmashelphaphosphataselocatedintheparasiteendoplasmicreticulumisrequiredforparasitevirulence AT mauldhlamarque toxoplasmashelphaphosphataselocatedintheparasiteendoplasmicreticulumisrequiredforparasitevirulence |