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大学・研究所にある論文を検索できる 「Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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Polyether ionophore kijimicin inhibits growth of Toxoplasma gondii and controls acute toxoplasmosis in mice

Leesombun Arpron Nihei Coh-ichi Kondoh Daisuke Nishikawa Yoshifumi 帯広畜産大学

2023.02.21

概要

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. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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参考文献

Antczak M, Dzitko K, Dlugonska H (2016) Human toxoplasmosis-Searching for novel chemotherapeutics. Biomed Pharmacother 82: 677-684.

Blais J, Beauchamp D, Chamberland S (1994) Azithromycin uptake and intracellular accumulation by Toxoplasma gondii-infected macrophages. J Antimicrob Chemother 34:371-382.

Carroll RW, Wainwright MS, Kim KY, Kidambi T, Gomez ND, Taylor T, Haldar K (2015) A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria. PLoS One 5: e13124.

Chapman HD, Jeffers TK, Williams RB (2010) Forty years of monensin for the control of coccidiosis in poultry. Poult Sci 89: 1788-1801.

Charvat RA, Arrizabalaga G (2016) Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function. Sci Rep 6: 22997.

Couzinet S, Dubremetz JF, Buzoni-Gatel D, Jeminet G, Prensier G (2000) In vitro activity of the polyether ionophorous antibiotic monensin against the cyst form of Toxoplasma gondii. Parasitology 121: 359-365.

Deljou M, Aslani MR, Mohri M, Movassaghi AR, Heidarpour M (2014) Clinical, laboratory and pathological findings in sub-acute monensin intoxication in goats. Vet Res Forum 5: 161- 167.

Dubey JP, Jones JL (2008) Toxoplasma gondii infection in humans and animals in the United States. Int J Parasitol 38: 1257-1278.

Harrell M, Carvounis PE (2014) Current treatment of toxoplasma retinochoroiditis: an evidence- based review. J Ophthalmol 2014: 273506.

Hermes G, Ajioka JW, Kelly KA, Mui E, Roberts F, Kasza K, Mayr T, Kirisits MJ, Wollmann R, Ferguson DJ, Roberts CW, Hwang JH, Trendler T, Kennan RP, Suzuki Y, Reardon C, Hickey WF, Chen L, McLeod R (2008) Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection. J Neuroinflammation 5: 48.

Huczynski A (2012) Polyether ionophores-promising bioactive molecules for cancer therapy. Bioorg Med Chem Lett 22: 7002-7010.

Kevin Ii DA, Meujo DA, Hamann MT (2009) Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites. Expert Opin Drug Discov 4:109-146.

Kirkbride CA, Dubey JP, Libal MC (1992) Effect of feeding lasalocid to pregnant ewes experimentally infected with Toxoplasma gondii. Vet Parasitol 44: 299-303.

Lavine MD, Arrizabalaga G (2011) The antibiotic monensin causes cell cycle disruption of Toxoplasma gondii mediated through the DNA repair enzyme TgMSH-1. Antimicrob Agents Chemother 55: 745-755.

Lavine MD, Arrizabalaga G (2012) Analysis of monensin sensitivity in Toxoplasma gondii reveals autophagy as a mechanism for drug induced death. PLoS One 7: e42107.

Leesombun A, Boonmasawai S, Shimoda N, Nishikawa Y (2016) Effects of Extracts from Thai Piperaceae Plants against Infection with Toxoplasma gondii. PLoS One 11: e0156116.

Leesombun A, Iijima M, Umeda K, Kondoh D, Pagmadulam B, Abdou AM, Suzuki Y, Ohba SI, Isshiki K, Kimura T, Kubota Y, Sawa R, Nihei CI, Nishikawa Y (2020) Metacytofilin is a potent therapeutic drug candidate for Toxoplasmosis. J Infect Dis 1221(5): 766-774.

Luder CG, Bohne W, Soldati D (2001) Toxoplasmosis: a persisting challenge. Trends Parasitol 17: 460-463.

Melton ML, Sheffield HG (1975) Activity of the anticoccidial compound, lasalocid, against Toxoplasma gondii in cultured cells. J Parasitol 61: 713-717.

Molina DA, Ramos GA, Zamora-Vélez A, Gallego-López GM, Rocha-Roa C, Gómez-Marin JE, Cortes E (2021) In vitro evaluation of new 4-thiazolidinones on invasion and growth of Toxoplasma gondii. Int J Parasitol Drugs Drug Resist 16:129-139.

Mollenhauer HH, Morre DJ, Rowe LD (1990) Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity. Biochim Biophys Acta 1031: 225-246.

Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363: 1965-1976.

Montoya JG, Remington JS (2008) Management of Toxoplasma gondii infection during pregnancy. Clin Infect Dis 47: 554-566.

Nakamura M, Kunimoto S, Takahashi Y, Naganawa H, Sakaue M, Inoue S, Ohno T, Takeuchi T (1992) Inhibitory effects of polyethers on human immunodeficiency virus replication. Antimicrob Agents Chemother 36: 492-494.

Nishikawa Y, Xuenan X, Makala L, Vielemeyer O, Joiner KA, Nagasawa H (2003) Characterisation of Toxoplasma gondii engineered to express mouse interferon-gamma. Int J Parasitol 33: 1525-1535.

Nishikawa Y, Zhang H, Ibrahim HM, Ui F, Ogiso A, Xuan X (2008) Construction of Toxoplasma gondii bradyzoite expressing the green fluorescent protein. Parasitol Int 57: 219-222.

Petersen E, Schmidt DR (2003) Sulfadiazine and pyrimethamine in the postnatal treatment of congenital toxoplasmosis: what are the options? Expert Rev Anti Infect Ther 1: 175-182.

Ricketts AP, Pfefferkorn ER (1993) Toxoplasma gondii: susceptibility and development of resistance to anticoccidial drugs in vitro. Antimicrob Agents Chemother 37: 2358-2363.

Rutkowski J, Brzezinski B (2013) Structures and properties of naturally occurring polyether antibiotics. Biomed Res Int 2013: 162513.

Sheffield HG, Melton ML (1975) Effect of pyrimethamine and sulfadiazine on the fine structure and multiplication of Toxoplasma gondii in cell cultures. J Parasitol 61:704-712.

Sibley LD, Khan A, Ajioka JW, Rosenthal BM (2009) Genetic diversity of Toxoplasma gondii in animals and humans. Philos Trans R Soc Lond B Biol Sci 364: 2749-2761.

Smith CK 2nd, Galloway, RB (1983) Influence of monensin on cation influx and glycolysis of Eimeria tenella sporozoites in vitro. J Parasitol 69: 666-670.

Smith CK 2nd, Galloway RB, White SL (1981) Effect of ionophores on survival, penetration, and development of Eimeria tenella sporozoites in vitro. J Parasitol 67: 511-516.

Souza AC, Machado FS, Celes MR, Faria G, Rocha LB, Silva JS, Rossi MA (2005) Mitochondrial damage as an early event of monensin-induced cell injury in cultured fibroblasts L929. J Vet Med A Physiol Pathol Clin Med 52: 230-237.

Takahashi Y, Nakamura H, Ogata R, Matsuda N, Hamada M, Naganawa H, Takita T, Iitaka Y, Sato K, Takeuchi T (1990) Kijimicin, a polyether antibiotic. J Antibiot 43: 441-443.

Tenter AM, Heckeroth AR, Weiss LM (2000) Toxoplasma gondii: from animals to humans. Int J Parasitol 30: 1217-1258.

Yamauchi T, Nakamura M, Honma H, Ikeda M, Kawashima K, Ohno T (1993) Mechanistic effects of kijimicin on inhibition of human immunodeficiency virus replication. Mol Cell Biochem 119: 35-41.

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