Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle

Article Article scientifique Article Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle eng 2025-03-01 author Chen Min 991308 Département de microbiologie et médecine moléculaire (MIMOL) author Koszti Szilamer 403620 author Bonavoglia Alessandro 931164 Département de microbiologie et médecine moléculaire (MIMOL) author Maco Bohumil 0000-0001-8444-313X 863802 Services communs de la faculté de médecine (SCMU) author Von Rohr Olivier 785914 Département de microbiologie et médecine moléculaire (MIMOL) author Peng Hong-Juan author Soldati-Favre Dominique 0000-0003-4156-2109 135114 Département de microbiologie et médecine moléculaire (MIMOL) author Kloehn Joachim 0000-0002-6366-8599 869011 Département de microbiologie et médecine moléculaire (MIMOL) 2095 10.1038/s41467-025-57302-x 40025025 2041-1723 https://www.nature.com/articles/s41467-025-57302-x The apicoplast, a relic plastid organelle derived from secondary endosymbiosis, is crucial for many medically relevant Apicomplexa. While it no longer performs photosynthesis, the organelle retains several essential metabolic pathways. In this study, we examine the four primary metabolic pathways in the Toxoplasma gondii apicoplast, along with an accessory pathway, and identify conditions that can bypass these. Contrary to the prevailing view that the apicoplast is indispensable for T. gondii , we demonstrate that bypassing all pathways renders the apicoplast non-essential. We further show that T. gondii lacking an apicoplast ( T. gondii −Apico ) can be maintained indefinitely in culture, establishing a unique model to study the functions of this organelle. Through comprehensive metabolomic, transcriptomic, and proteomic analyses of T. gondii −Apico we uncover significant adaptation mechanisms following loss of the organelle and identify numerous putative apicoplast proteins revealed by their decreased abundance in T. gondii −Apico . Moreover, T. gondii −Apico parasites exhibit reduced sensitivity to apicoplast targeting compounds, providing a valuable tool for discovering new drugs acting on the organelle. The capability to culture T. gondii without its plastid offers new avenues for exploring apicoplast biology and developing novel therapeutic strategies against apicomplexan parasites. Animals Apicoplasts / genetics Apicoplasts / metabolism Metabolic Networks and Pathways / genetics Proteomics Protozoan Proteins / genetics Protozoan Proteins / metabolism Toxoplasma / genetics Toxoplasma / growth & development Toxoplasma / metabolism Dewey 616 Novartis Stiftung für Medizinisch-Biologische Forschung #22C164 Gertrude von Meissner-Stiftung NA Swiss National Science Foundation Infiltrating the vital metabolite transportome of the vestigal plastid of Apicomplexa 216166 CH Programmes Swiss National Science Foundation A comprehensive characterization of key organellar metabolic transporters in Apicomplexa to enter in the drug discovery pipeline 200277 CH Programmes 54 Département de microbiologie et médecine moléculaire 21B false 443 Biologie d'un parasite intracellulaire obligatoire 773 https://yareta.unige.ch/archives/e01180fc-3de8-49da-a86d-ffbebf67bbce https://yareta.unige.ch/archives/9d1b1f28-0c72-481e-a52d-da644b203eb7 Nature communications 16 1 e7f46811-457c-4514-8e47-909515fc1c06 Article (Published version) Public Article_scientifique_from_crossref.pdf 7995121 application/pdf CC BY-4.0 6eed9554f6fc775bfac58f62842e7f429fe17368f6a22d011aed786915902075 865300e4-9ad7-4f65-9f9f-2c7bb2a8aead Supplemental data Public 41467_2025_57302_MOESM1_ESM.pdf 2058784 application/pdf 83a73db10e7f49d55aa9625b2db061d4a02705a48c2ab0d2cefbd27f1719ac9b 637cb72e-167b-450b-80b0-988aaa36157d Supplemental data Public 41467_2025_57302_MOESM2_ESM.pdf 104055 application/pdf 28b09bb9c1765df89c4b370b4609336ac0cb83499bce086dc5185c580c5c17fc ffbc541c-ea17-46b7-8275-87fb6c8c4171 Supplemental data Public 41467_2025_57302_MOESM3_ESM.docx 23641 application/vnd.openxmlformats-officedocument.wordprocessingml.document 30ec31bea392b0df0bff4cf3b56a1f73ae8ad34033e69eb61d01359497892b16 808431da-03cc-4c91-92a1-9b2b62b5f9be Supplemental data Public 41467_2025_57302_MOESM4_ESM.xlsx 21514 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 433f04733da70e17e2beda345544b65a772ff893428067af1011e9561b5527fa 0245bbb7-1a8f-431c-9764-f30ce1d77f59 Supplemental data Public 41467_2025_57302_MOESM5_ESM.xlsx 186282 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 52a4c3b4e43a5e315c49848d7bc0a21fe36fe1f2516aaa595768c7db75b3ed26 7de0a4ed-b461-42ce-8444-fb79d28d7d87 Supplemental data Public 41467_2025_57302_MOESM6_ESM.xlsx 31637 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 82d1fdd16eecea202302ea39b930ef52e1a2f86f77995854f4ce650a9702c1e8 2636dbac-d996-4e69-8368-2e05721ff946 Supplemental data Public 41467_2025_57302_MOESM7_ESM.xlsx 2098238 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet fb9b953a6f0324c133fb05f6c266a80f1219e763939f7e62b2c81a0e1b3c0706 3a891f9f-6121-4106-a4ae-953b90c2b3e9 Supplemental data Public 41467_2025_57302_MOESM8_ESM.xlsx 3758812 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 2b15a90133d189752a3b025c211977631a0006742538bc2664fa791b74323725 3f1b2efd-8194-4793-a24a-272a747358ad Supplemental data Public 41467_2025_57302_MOESM9_ESM.pdf 2023525 application/pdf 5272e2915919d45e4062bbc8151e5ad97a48f6cfbdcb036199551bea3a97f672 e1bda75f-e32a-45fa-9dc0-50eea48d2d1c Supplemental data Public 41467_2025_57302_MOESM10_ESM.pdf 380580 application/pdf aea40ea085c9284581469d05ed328b73cc1a8ab24041c0c4478b1a071b62c989 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle	Nature communications			2025	206	106

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Koszti, Szilamer