title: Toxoplasma gondii autophagy-related protein ATG9 is crucial for the survival of parasites in their host.
abstract: Autophagy is a conserved, life-promoting, catabolic process involved in the recycling of nonessential cellular components in response to stress. The parasite Toxoplasma gondii is an early-diverging eukaryote in which part of the autophagy machinery is not exclusively involved in a catabolic process but instead has been repurposed for an original function in organelle inheritance during cell division. This function, depending essentially on protein TgATG8 and its membrane conjugation system, is crucial for parasite survival and prevented an in depth study of autophagy in the mutants generated so far in Toxoplasma. Thus, in order to decipher the primary function of canonical autophagy in the parasites, we generated a cell line deficient for TgATG9, a protein thought to be involved in the early steps of the autophagy process. Although the protein proved to be dispensable for the development of these obligate intracellular parasites in vitro, the absence of TgATG9 led to a reduced ability to sustain prolonged extracellular stress. Importantly, depletion of the protein significantly reduced parasites survival in macrophages and markedly attenuated their virulence in mice. Altogether, this shows TgATG9 is important for the fate of Toxoplasma in immune cells and contributes to the overall virulence of the parasite, possibly through an involvement in a canonical autophagy pathway.
authors.affiliation: DIMNP-UMR 5235 CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Hoa Mai
authors.initials: HM
authors.lastname: Nguyen
authors.affiliation: Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hiba
authors.initials: H
authors.lastname: El Hajj
authors.affiliation: Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Rana
authors.initials: R
authors.lastname: El Hajj
authors.affiliation: Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Nadim
authors.initials: N
authors.lastname: Tawil
authors.affiliation: DIMNP-UMR 5235 CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Berry
authors.affiliation: DIMNP-UMR 5235 CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Lebrun
authors.affiliation: DIMNP-UMR 5235 CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Bordat
authors.affiliation: DIMNP-UMR 5235 CNRS, Université de Montpellier, Montpellier, France.
authors.forename: Sébastien
authors.identifier: 0000-0003-1853-1494
authors.initials: S
authors.lastname: Besteiro
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D000071183:Autophagy-Related Proteins / Q000235:genetics*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D005260:Female; D055786:Gene Knockout Techniques; D008264:Macrophages / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics*; D014122:Toxoplasma / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: C000625877:ATG9 protein, Toxoplasma gondii; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D015800:Protozoan Proteins
keywords: ATG9; autophagy; stress response; toxoplasma; virulence