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Scientific article
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English

Fundamental Roles of the Golgi-Associated Toxoplasma Aspartyl Protease, ASP5, at the Host-Parasite Interface

Contributors

Hammoudi, Pierre-Mehdi; Jacot, Damien; Mueller, Christina; Di Cristina, Manlio; Dogga, Sunil Kumar; Marq, Jean-Baptiste; Romano, Julia; Tosetti, Nicolo; Dubrot Armendariz, Juan; Emre, Yalin; Lunghi, Matteo; Coppens, Isabelle; Yamamoto, Masahiro; Sojka, Daniel; Pino, Paco; Soldati-Favre, Dominique

Published in

PLOS pathogens, vol. 11, no. 10, e1005211

Publication date

2015

Abstract

Toxoplasma gondii possesses sets of dense granule proteins (GRAs) that either assemble at, or cross the parasitophorous vacuole membrane (PVM) and exhibit motifs resembling the HT/PEXEL previously identified in a repertoire of exported Plasmodium proteins. Within Plasmodium spp., cleavage of the HT/PEXEL motif by the endoplasmic reticulum-resident protease Plasmepsin V precedes trafficking to and export across the PVM of proteins involved in pathogenicity and host cell remodelling. Here, we have functionally characterized the T. gondii aspartyl protease 5 (ASP5), a Golgi-resident protease that is phylogenetically related to Plasmepsin V. We show that deletion of ASP5 causes a significant loss in parasite fitness in vitro and an altered virulence in vivo. Furthermore, we reveal that ASP5 is necessary for the cleavage of GRA16, GRA19 and GRA20 at the PEXEL-like motif. In the absence of ASP5, the intravacuolar nanotubular network disappears and several GRAs fail to localize to the PVM, while GRA16 and GRA24, both known to be targeted to the host cell nucleus, are retained within the vacuolar space. Additionally, hypermigration of dendritic cells and bradyzoite cyst wall formation are impaired, critically impacting on parasite dissemination and persistence. Overall, the absence of ASP5 dramatically compromises the parasite's ability to modulate host signalling pathways and immune responses.

UNIGE affiliation entities

UNIGE research groups

Funding

  • Swiss National Science Foundation - FN3100A0-116722

Citation (ISO format)

HAMMOUDI, Pierre-Mehdi et al. Fundamental Roles of the Golgi-Associated Toxoplasma Aspartyl Protease, ASP5, at the Host-Parasite Interface. In: PLOS pathogens, 2015, vol. 11, n° 10, p. e1005211. doi: 10.1371/journal.ppat.1005211

Main files (1)

Article (Accepted version)

Identifiers

Journal ISSN

1553-7366
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375downloads

Technical informations

Creation

17/10/2015 16:10:00

First validation

17/10/2015 16:10:00

Update

14/03/2023 23:50:00

Status update

14/03/2023 23:50:00

Last indexation

31/10/2024 01:55:29
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