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

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, the authors 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, they demonstrate that bypassing all pathways renders the apicoplast non-essential. They 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 the authors 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.

Read the full article in Nature Communications: https://www.nature.com/articles/s41467-025-57302-x

WHY IS this important?

The apicoplast is an organelle found in parasites such as Toxoplasma gondii and plays a vital role in their survival. It is responsible for the production of essential molecules such as fatty acids, haem and isoprenoids. This study aimed to investigate whether T. gondii could survive without the apicoplast by providing it with alternative sources of these molecules. The results showed that the organelle’s functions can be bypassed, enabling for the first time the cultivation of T. gondii without its apicoplast. The analysis of parasites lacking the organelle opens up new opportunities for drug development, offering a potential strategy for controlling diseases caused by T. gondii, including human and animal toxoplasmosis, as well as malaria and other apicomplexan diseases.

Citation: 

Chen, M., Koszti, S.G., Bonavoglia, A. et al. Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle. Nat Commun 16, 2095 (2025). https://doi.org/10.1038/s41467-025-57302-x​​​​​​​

Funding:

This work is supported by the Swiss National Science Foundation, the National Natural Science Foundation of China, a generous donor advised by CARIGEST SA, the Novartis Foundation for Medical Biological Research and funding from the Foundation Gertrude von Meissner.

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