The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondii
Toxoplasma gondii (T. gondii), an apicomplexan parasite, infects a wide range of warm-blooded animals and poses significant risks to human health. The fatty acid synthesis II (FASII) pathway in the apicoplast, which is the major source of fatty acids in parasites, is considered a potential drug targ...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1542122/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850166054870843392 |
|---|---|
| author | Ke Pan Ao Zeng Xiaodie Ruan Xinyu Mo Bang Shen Junlong Zhao Yanqin Zhou |
| author_facet | Ke Pan Ao Zeng Xiaodie Ruan Xinyu Mo Bang Shen Junlong Zhao Yanqin Zhou |
| author_sort | Ke Pan |
| collection | DOAJ |
| description | Toxoplasma gondii (T. gondii), an apicomplexan parasite, infects a wide range of warm-blooded animals and poses significant risks to human health. The fatty acid synthesis II (FASII) pathway in the apicoplast, which is the major source of fatty acids in parasites, is considered a potential drug target. The apicoplast also harbors some enzymes of central carbon metabolism, which are crucial for its survival, but their biological roles remain unclear. In this study, we focused on apicoplast-localized isocitrate dehydrogenase 1 (ICDH1) and deleted it using CRISPR-Cas9 technology. The Δicdh1 mutant tachyzoites displayed markedly impaired growth kinetics, with further suppression under serum-deprived conditions. However, this deletion did not affect the viability or virulence of the Δicdh1 mutant in mice. NADPH, a product of ICDH1-mediated decarboxylation of isocitrate, is an essential cofactor for fatty acid synthesis. Using ¹³C6 glucose as a metabolic carbon source, we showed that the mutant strains had reduced incorporation of glucose-derived carbons into medium-chain length fatty acids (C14:0 and C16:0). Additionally, the growth of the mutant was partially restored by supplementation with exogenous C14:0 and C16:0 fatty acids. These results indicate that ICDH1 deletion affects the FASII pathway and parasite growth. Consistent with previous studies, this study confirms that T. gondii has metabolic flexibility in the apicoplast that allows it to acquire fatty acids through various pathways. |
| format | Article |
| id | doaj-art-bec33bc0cadf450a9957d2672fe5d076 |
| institution | OA Journals |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-bec33bc0cadf450a9957d2672fe5d0762025-08-20T02:21:34ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-06-011510.3389/fcimb.2025.15421221542122The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondiiKe PanAo ZengXiaodie RuanXinyu MoBang ShenJunlong ZhaoYanqin ZhouToxoplasma gondii (T. gondii), an apicomplexan parasite, infects a wide range of warm-blooded animals and poses significant risks to human health. The fatty acid synthesis II (FASII) pathway in the apicoplast, which is the major source of fatty acids in parasites, is considered a potential drug target. The apicoplast also harbors some enzymes of central carbon metabolism, which are crucial for its survival, but their biological roles remain unclear. In this study, we focused on apicoplast-localized isocitrate dehydrogenase 1 (ICDH1) and deleted it using CRISPR-Cas9 technology. The Δicdh1 mutant tachyzoites displayed markedly impaired growth kinetics, with further suppression under serum-deprived conditions. However, this deletion did not affect the viability or virulence of the Δicdh1 mutant in mice. NADPH, a product of ICDH1-mediated decarboxylation of isocitrate, is an essential cofactor for fatty acid synthesis. Using ¹³C6 glucose as a metabolic carbon source, we showed that the mutant strains had reduced incorporation of glucose-derived carbons into medium-chain length fatty acids (C14:0 and C16:0). Additionally, the growth of the mutant was partially restored by supplementation with exogenous C14:0 and C16:0 fatty acids. These results indicate that ICDH1 deletion affects the FASII pathway and parasite growth. Consistent with previous studies, this study confirms that T. gondii has metabolic flexibility in the apicoplast that allows it to acquire fatty acids through various pathways.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1542122/fullToxoplasma gondiiapicoplastisocitrate dehydrogensasemetabolismFAS 2 |
| spellingShingle | Ke Pan Ao Zeng Xiaodie Ruan Xinyu Mo Bang Shen Junlong Zhao Yanqin Zhou The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondii Frontiers in Cellular and Infection Microbiology Toxoplasma gondii apicoplast isocitrate dehydrogensase metabolism FAS 2 |
| title | The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondii |
| title_full | The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondii |
| title_fullStr | The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondii |
| title_full_unstemmed | The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondii |
| title_short | The apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of Toxoplasma gondii |
| title_sort | apicoplast localized isocitrate dehydrogenase is needed for de novo fatty acid synthesis in the apicoplast of toxoplasma gondii |
| topic | Toxoplasma gondii apicoplast isocitrate dehydrogensase metabolism FAS 2 |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1542122/full |
| work_keys_str_mv | AT kepan theapicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT aozeng theapicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT xiaodieruan theapicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT xinyumo theapicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT bangshen theapicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT junlongzhao theapicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT yanqinzhou theapicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT kepan apicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT aozeng apicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT xiaodieruan apicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT xinyumo apicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT bangshen apicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT junlongzhao apicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii AT yanqinzhou apicoplastlocalizedisocitratedehydrogenaseisneededfordenovofattyacidsynthesisintheapicoplastoftoxoplasmagondii |