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ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence

Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be responsible for transmission of T. gondii to...

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Autores principales: Singh, Shishir, Murillo-León, Mateo, Endres, Niklas Sebastian, Arenas Soto, Ailan Farid, Gómez-Marín, Jorge Enrique, Melbert, Florence, Kanneganti, Thirumala-Devi, Yamamoto, Masahiro, Campos, Claudia, Howard, Jonathan Charles, Taylor, Gregory Alan, Steinfeldt, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848475/
https://www.ncbi.nlm.nih.gov/pubmed/36603017
http://dx.doi.org/10.1371/journal.ppat.1011003
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author Singh, Shishir
Murillo-León, Mateo
Endres, Niklas Sebastian
Arenas Soto, Ailan Farid
Gómez-Marín, Jorge Enrique
Melbert, Florence
Kanneganti, Thirumala-Devi
Yamamoto, Masahiro
Campos, Claudia
Howard, Jonathan Charles
Taylor, Gregory Alan
Steinfeldt, Tobias
author_facet Singh, Shishir
Murillo-León, Mateo
Endres, Niklas Sebastian
Arenas Soto, Ailan Farid
Gómez-Marín, Jorge Enrique
Melbert, Florence
Kanneganti, Thirumala-Devi
Yamamoto, Masahiro
Campos, Claudia
Howard, Jonathan Charles
Taylor, Gregory Alan
Steinfeldt, Tobias
author_sort Singh, Shishir
collection PubMed
description Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be responsible for transmission of T. gondii to the domestic cat, its definitive host. Interferon-inducible Immunity-Related GTPases (IRG proteins) are important for control of murine T. gondii infections. Virulence differences between T. gondii strains are linked to polymorphic rhoptry proteins (ROPs) that cooperate to inactivate individual IRG family members. In particular, the pseudokinase ROP5 isoform B is critically important in laboratory strains of mice. We identified T. gondii ROP39 in complex with ROP5B and demonstrate its contribution to acute T. gondii virulence. ROP39 directly targets Irgb10 and inhibits homodimer formation of the GTPase leading to an overall reduction of IRG protein loading onto the parasitophorous vacuolar membrane (PVM). Maintenance of PVM integrity rescues the parasite from IRG protein-mediated clearance in vitro and in vivo. This study identifies a novel T. gondii effector that is important for specific inactivation of the IRG resistance system. Our data reveal that yet unknown T. gondii effectors can emerge from identification of direct interaction partners of ROP5B.
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spelling pubmed-98484752023-01-19 ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence Singh, Shishir Murillo-León, Mateo Endres, Niklas Sebastian Arenas Soto, Ailan Farid Gómez-Marín, Jorge Enrique Melbert, Florence Kanneganti, Thirumala-Devi Yamamoto, Masahiro Campos, Claudia Howard, Jonathan Charles Taylor, Gregory Alan Steinfeldt, Tobias PLoS Pathog Research Article Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be responsible for transmission of T. gondii to the domestic cat, its definitive host. Interferon-inducible Immunity-Related GTPases (IRG proteins) are important for control of murine T. gondii infections. Virulence differences between T. gondii strains are linked to polymorphic rhoptry proteins (ROPs) that cooperate to inactivate individual IRG family members. In particular, the pseudokinase ROP5 isoform B is critically important in laboratory strains of mice. We identified T. gondii ROP39 in complex with ROP5B and demonstrate its contribution to acute T. gondii virulence. ROP39 directly targets Irgb10 and inhibits homodimer formation of the GTPase leading to an overall reduction of IRG protein loading onto the parasitophorous vacuolar membrane (PVM). Maintenance of PVM integrity rescues the parasite from IRG protein-mediated clearance in vitro and in vivo. This study identifies a novel T. gondii effector that is important for specific inactivation of the IRG resistance system. Our data reveal that yet unknown T. gondii effectors can emerge from identification of direct interaction partners of ROP5B. Public Library of Science 2023-01-05 /pmc/articles/PMC9848475/ /pubmed/36603017 http://dx.doi.org/10.1371/journal.ppat.1011003 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Singh, Shishir
Murillo-León, Mateo
Endres, Niklas Sebastian
Arenas Soto, Ailan Farid
Gómez-Marín, Jorge Enrique
Melbert, Florence
Kanneganti, Thirumala-Devi
Yamamoto, Masahiro
Campos, Claudia
Howard, Jonathan Charles
Taylor, Gregory Alan
Steinfeldt, Tobias
ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence
title ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence
title_full ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence
title_fullStr ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence
title_full_unstemmed ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence
title_short ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence
title_sort rop39 is an irgb10-specific parasite effector that modulates acute toxoplasma gondii virulence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848475/
https://www.ncbi.nlm.nih.gov/pubmed/36603017
http://dx.doi.org/10.1371/journal.ppat.1011003
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