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Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies.
Parasitol Int. 2010 Dec; 59(4):560-4.PI

Abstract

Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or "sleeping sickness," which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC(50) value: 1 nM) to eliminate trypanosomes in human infective strain cultures.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Nakamura K
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Tokyo 113-0033, Japan. kosnakamura@nihs.go.jp
Fujioka S
No affiliation info available
Fukumoto S
No affiliation info available
Inoue N
No affiliation info available
Sakamoto K
No affiliation info available
Hirata H
No affiliation info available
Kido Y
No affiliation info available
Yabu Y
No affiliation info available
Suzuki T
No affiliation info available
Watanabe Y
No affiliation info available
Saimoto H
No affiliation info available
Akiyama H
No affiliation info available
Kita K
No affiliation info available

MeSH

Amino Acid SequenceAnimalsConserved SequenceEnzyme InhibitorsHumansMitochondrial ProteinsMolecular Sequence DataOxidoreductasesParasitic Sensitivity TestsPlant ProteinsProtozoan ProteinsSequence AlignmentSequence Analysis, DNASesquiterpenesTrypanosoma brucei bruceiTrypanosoma brucei gambienseTrypanosoma brucei rhodesienseTrypanosomiasis, African

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20688188

Citation

Nakamura, Kosuke, et al. "Trypanosome Alternative Oxidase, a Potential Therapeutic Target for Sleeping Sickness, Is Conserved Among Trypanosoma Brucei Subspecies." Parasitology International, vol. 59, no. 4, 2010, pp. 560-4.
Nakamura K, Fujioka S, Fukumoto S, et al. Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies. Parasitol Int. 2010;59(4):560-4.
Nakamura, K., Fujioka, S., Fukumoto, S., Inoue, N., Sakamoto, K., Hirata, H., Kido, Y., Yabu, Y., Suzuki, T., Watanabe, Y., Saimoto, H., Akiyama, H., & Kita, K. (2010). Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies. Parasitology International, 59(4), 560-4. https://doi.org/10.1016/j.parint.2010.07.006
Nakamura K, et al. Trypanosome Alternative Oxidase, a Potential Therapeutic Target for Sleeping Sickness, Is Conserved Among Trypanosoma Brucei Subspecies. Parasitol Int. 2010;59(4):560-4. PubMed PMID: 20688188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies. AU - Nakamura,Kosuke, AU - Fujioka,Sunao, AU - Fukumoto,Shinya, AU - Inoue,Noboru, AU - Sakamoto,Kimitoshi, AU - Hirata,Haruyuki, AU - Kido,Yasutoshi, AU - Yabu,Yoshisada, AU - Suzuki,Takashi, AU - Watanabe,Yoh-ichi, AU - Saimoto,Hiroyuki, AU - Akiyama,Hiroshi, AU - Kita,Kiyoshi, Y1 - 2010/08/03/ PY - 2010/06/26/received PY - 2010/07/17/revised PY - 2010/07/23/accepted PY - 2010/8/7/entrez PY - 2010/8/7/pubmed PY - 2011/2/24/medline SP - 560 EP - 4 JF - Parasitology international JO - Parasitol Int VL - 59 IS - 4 N2 - Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or "sleeping sickness," which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC(50) value: 1 nM) to eliminate trypanosomes in human infective strain cultures. SN - 1873-0329 UR - https://www.unboundmedicine.com/medline/citation/20688188/Trypanosome_alternative_oxidase_a_potential_therapeutic_target_for_sleeping_sickness_is_conserved_among_Trypanosoma_brucei_subspecies_ DB - PRIME DP - Unbound Medicine ER -