Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice
Issued Date
2022-01-01
Resource Type
ISSN
09320113
eISSN
14321955
Scopus ID
2-s2.0-85118654513
Pubmed ID
34750652
Journal Title
Parasitology Research
Volume
121
Issue
1
Start Page
413
End Page
422
Rights Holder(s)
SCOPUS
Bibliographic Citation
Parasitology Research Vol.121 No.1 (2022) , 413-422
Suggested Citation
Leesombun A., Nihei C.i., Kondoh D., Nishikawa Y. Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice. Parasitology Research Vol.121 No.1 (2022) , 413-422. 422. doi:10.1007/s00436-021-07363-w Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83401
Title
Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice
Author(s)
Other Contributor(s)
Abstract
The natural polyether ionophore antibiotics may be important chemotherapeutic agents. Among them, kijimicin represents an important type of ionophore compound because it inhibits Eimeria tenella and human immunodeficiency virus. The ionophore monensin displays potent activities against several coccidian parasites including the opportunistic pathogen of humans, Toxoplasma gondii. At first, we evaluated the anti-Toxoplasma activity of kijimicin, monensin as a reference control, and anti-Toxoplasma drugs such as clindamycin, in vitro. The half inhibitory concentrations (IC50) for the anti-Toxoplasma activities of kijimicin, monensin, and clindamycin were 45.6 ± 2.4 nM, 1.3 ± 1.8 nM, and 238.5 ± 1.8 nM, respectively. Morphological analyses by electron microscopy revealed cellular swelling and multiple intracellular vacuole-like structures in the T. gondii tachyzoites after treatment with kijimicin and monensin. Kijimicin and monensin also inhibited the invasion of extracellular parasites (IC50 = 216.6 ± 1.9 pM and 531.1 ± 1.9 pM, respectively). Importantly, kijimicin treatment resulted in decreased mitochondrial membrane potential and generation of reactive oxygen species in T. gondii as monensin did. Furthermore, mice treated with kijimicin at 10 mg/kg/day and 3 mg/kg/day showed 91.7% and 66.7% survival rates, respectively, 30 days after infection with T. gondii. The control mice all died within 18 days of infection. The present study shows that kijimicin inhibits T. gondii growth and changes the ultrastruct of the parasites. This finding may lead to validation of kijimicin as new drug to control T. gondii growth.