Review
doi: 10.1016/j.drup.2003.09.001.
Drug transport and drug resistance in African trypanosomes
Affiliations
- PMID: 14643298
- DOI: 10.1016/j.drup.2003.09.001
Item in Clipboard
Review
Drug transport and drug resistance in African trypanosomes
Drug Resist Updat.
2003 Oct.
Abstract
Drug resistance in African trypanosomes has been studied for almost a hundred years. Beginning with Paul Ehrlich's work that led to the chemoreceptor hypothesis, reduction of net drug uptake has emerged as the most frequent cause of resistance. This review, therefore, focuses on trypanosomal drug transporter genes. TbAT1 encodes purine permease P2, which mediates influx of melarsoprol and diamidines. Disruption of TbAT1 in Trypanosoma brucei reduced sensitivity to these trypanocides. TbMRPA encodes a putative trypanothione-conjugate efflux pump, and overexpression of TbMRPA in T. brucei causes melarsoprol resistance. It will be important to determine the role of TbAT1 and TbMRPA in sleeping sickness treatment failures.
Similar articles
-
Development of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Treatment of human African trypanosomiasis with natural products (Review).Int J Mol Med. 2008 Oct;22(4):411-9. Int J Mol Med. 2008. PMID: 18813846 Review.
-
Genotypic and phenotypic characterization of Trypanosoma brucei gambiense isolates from Ibba, South Sudan, an area of high melarsoprol treatment failure rate.Acta Trop. 2007 Nov-Dec;104(2-3):84-90. doi: 10.1016/j.actatropica.2007.07.007. Epub 2007 Aug 1. Acta Trop. 2007. PMID: 17765860
-
Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol.PLoS Negl Trop Dis. 2013 Oct 10;7(10):e2475. doi: 10.1371/journal.pntd.0002475. eCollection 2013. PLoS Negl Trop Dis. 2013. PMID: 24130910 Free PMC article.
-
Chemotherapeutic strategies against Trypanosoma brucei: drug targets vs. drug targeting.Curr Pharm Des. 2007;13(6):555-67. doi: 10.2174/138161207780162809. Curr Pharm Des. 2007. PMID: 17346174 Review.
-
Target-based drug discovery for human African trypanosomiasis: selection of molecular target and chemical matter.Parasitology. 2014 Jan;141(1):28-36. doi: 10.1017/S0031182013001017. Epub 2013 Aug 9. Parasitology. 2014. PMID: 23931634 Free PMC article. Review.
Cited by
-
Identification and characterization of the three members of the CLC family of anion transport proteins in Trypanosoma brucei.PLoS One. 2017 Dec 15;12(12):e0188219. doi: 10.1371/journal.pone.0188219. eCollection 2017. PLoS One. 2017. PMID: 29244877 Free PMC article.
-
Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes.Int J Parasitol Drugs Drug Resist. 2017 Dec;7(3):303-313. doi: 10.1016/j.ijpddr.2017.08.001. Epub 2017 Aug 12. Int J Parasitol Drugs Drug Resist. 2017. PMID: 28826037 Free PMC article.
-
Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness.J Med Chem. 2010 Jul 8;53(13):5025-32. doi: 10.1021/jm100456a. J Med Chem. 2010. PMID: 20527952 Free PMC article.
-
Discovery of drug-like inhibitors of an essential RNA-editing ligase in Trypanosoma brucei.Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17278-83. doi: 10.1073/pnas.0805820105. Epub 2008 Nov 3. Proc Natl Acad Sci U S A. 2008. PMID: 18981420 Free PMC article.
-
DNA repair pathways in trypanosomatids: from DNA repair to drug resistance.Microbiol Mol Biol Rev. 2014 Mar;78(1):40-73. doi: 10.1128/MMBR.00045-13. Microbiol Mol Biol Rev. 2014. PMID: 24600040 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
