1. An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei
- Author
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Yoshisada Yabu, Kiyoshi Kita, Kazuo Nagai, Shigeru Sakajo, Akio Yoshimoto, Nobuko Minagawa, Keiichi Meguro, and Nobuo Ohta
- Subjects
Glycerol ,Male ,Alternative oxidase ,Ubiquinol ,Ubiquinone ,Cellular respiration ,Trypanosoma brucei brucei ,Dehydrogenase ,In Vitro Techniques ,Biology ,Mitochondrion ,Trypanosoma brucei ,Microbiology ,Electron Transport ,Mice ,chemistry.chemical_compound ,Oxygen Consumption ,Animals ,Rats, Wistar ,Molecular Biology ,chemistry.chemical_classification ,biology.organism_classification ,Trypanocidal Agents ,Anti-Bacterial Agents ,Mitochondria ,Rats ,Glucose ,Trypanosomiasis, African ,Infectious Diseases ,Enzyme ,Biochemistry ,chemistry ,Ascofuranone ,Glycerophosphates ,Parasitology ,Energy Metabolism ,Oxidation-Reduction ,Sesquiterpenes - Abstract
Ascofuranone, a prenylphenol antibiotic isolated from a phytopathogenic fungus, Ascochyta visiae, strongly inhibited both glucose-dependent cellular respiration and glycerol-3-phosphate-dependent mitochondrial O2 consumption of long slender bloodstream forms of Trypanosoma brucei brucei. This inhibition was suggested to be due to inhibition of the mitochondria electron-transport system, composed of glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) and plant-like alternative oxidase. Ascofuranone noncompetitively inhibited the reduced coenzyme Q1-dependent O2 uptake of the mitochondria with respect to ubiquinol (Ki=2.38 nM). Therefore, the susceptible site is deduced to be the ubiquinone redox machinery which links the two enzyme activities. Further, ascofuranone in combination with glycerol completely blocked energy production, and potently inhibited the in vitro growth of the parasite. Our findings suggest that ascofuranone might be a promising candidate for the chemotherapeutic agents of African trypanosomiasis.
- Published
- 1997
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