Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice
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 cocci...
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th-mahidol.731612022-08-04T11:56:37Z Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice Arpron Leesombun Coh ichi Nihei Daisuke Kondoh Yoshifumi Nishikawa Microbial Chemistry Research Center Mahidol University Obihiro University of Agriculture and Veterinary Medicine Agricultural and Biological Sciences Immunology and Microbiology Medicine Veterinary 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. 2022-08-04T03:37:33Z 2022-08-04T03:37:33Z 2022-01-01 Article Parasitology Research. Vol.121, No.1 (2022), 413-422 10.1007/s00436-021-07363-w 14321955 09320113 2-s2.0-85118654513 https://repository.li.mahidol.ac.th/handle/123456789/73161 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85118654513&origin=inward |
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Agricultural and Biological Sciences Immunology and Microbiology Medicine Veterinary Arpron Leesombun Coh ichi Nihei Daisuke Kondoh Yoshifumi Nishikawa Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice |
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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. |
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Microbial Chemistry Research Center |
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Microbial Chemistry Research Center Arpron Leesombun Coh ichi Nihei Daisuke Kondoh Yoshifumi Nishikawa |
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Article |
author |
Arpron Leesombun Coh ichi Nihei Daisuke Kondoh Yoshifumi Nishikawa |
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Arpron Leesombun |
title |
Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice |
title_short |
Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice |
title_full |
Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice |
title_fullStr |
Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice |
title_full_unstemmed |
Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice |
title_sort |
polyether ionophore kijimicin inhibits growth of toxoplasma gondii and controls acute toxoplasmosis in mice |
publishDate |
2022 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/73161 |
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1763497510964297728 |