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Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle
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Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle
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Journal Article
Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle
2025
Overview
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.
Here, Chen et al. bypass the critical metabolic pathways of the remnant plastid organelle of
Toxoplasma gondii
. A subsequent detailed characterization of parasites devoid of the apicoplast organelle provides unprecedented insights into its constituents, evolution and functions, uncovering new vulnerabilities.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
