Publication: Metacytofilin Is a Potent Therapeutic Drug Candidate for Toxoplasmosis
Issued Date
2020-02-18
Resource Type
ISSN
15376613
00221899
00221899
Other identifier(s)
2-s2.0-85081684993
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Infectious Diseases. Vol.221, No.5 (2020), 766-774
Suggested Citation
Arpron Leesombun, Masatomi Iijima, Kousuke Umeda, Daisuke Kondoh, Baldorj Pagmadulam, Ahmed M. Abdou, Yutaka Suzuki, Shun Ichi Ohba, Kunio Isshiki, Tomoyuki Kimura, Yumiko Kubota, Ryuichi Sawa, Coh Ichi Nihei, Yoshifumi Nishikawa Metacytofilin Is a Potent Therapeutic Drug Candidate for Toxoplasmosis. Journal of Infectious Diseases. Vol.221, No.5 (2020), 766-774. doi:10.1093/infdis/jiz501 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/53754
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Title
Metacytofilin Is a Potent Therapeutic Drug Candidate for Toxoplasmosis
Abstract
© 2019 The Author(s). Background: Toxoplasmosis, a parasitic disease caused by Toxoplasma gondii, is an important cause of miscarriage or adverse fetal effects, including neurological and ocular manifestations in humans. Current anti-Toxoplasma drugs have limited efficacy against toxoplasmosis and also have severe side effects. Therefore, novel efficacious drugs are urgently needed. Here, we identified metacytofilin (MCF) from a fungal Metarhizium species as a potential anti-Toxoplasma compound. Methods: Anti-Toxoplasma activities of MCF and its derivatives were evaluated in vitro and in vivo using nonpregnant and pregnant mice. To understand the mode of action of MCF, the RNA expression of host and parasite genes was investigated by RNAseq. Results: In vitro, MCF inhibited the viability of intracellular and extracellular T. gondii. Administering MCF intraperitoneally or orally to mice after infection with T. gondii tachyzoites increased mouse survival compared with the untreated animals. Remarkably, oral administration of MCF to pregnant mice prevented vertical transmission of the parasite. Interestingly, RNA sequencing of T. gondii-infected cells treated with MCF showed that MCF inhibited DNA replication and enhanced RNA degradation in the parasites. Conclusions: With its potent anti-T. gondii activity, MCF is a strong candidate for future drug development against toxoplasmosis.