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- Title
Metacytofilin Is a Potent Therapeutic Drug Candidate for Toxoplasmosis.
- Authors
Leesombun, Arpron; Iijima, Masatomi; Umeda, Kousuke; Kondoh, Daisuke; Pagmadulam, Baldorj; Abdou, Ahmed M; Suzuki, Yutaka; Ohba, Shun-Ichi; Isshiki, Kunio; Kimura, Tomoyuki; Kubota, Yumiko; Sawa, Ryuichi; Nihei, Coh-Ichi; Nishikawa, Yoshifumi
- Abstract
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.
- Subjects
TOXOPLASMOSIS; DNA replication; PARASITIC diseases; TOXOPLASMA gondii; TOXOPLASMOSIS treatment; METARHIZIUM; GENE expression; ANTIPARASITIC agents
- Publication
Journal of Infectious Diseases, 2020, Vol 221, Issue 5, p766
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jiz501