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Genetic dissection of drug resistance in trypanosomes

The trypanosomes cause two neglected tropical diseases, Chagas disease in the Americas and African trypanosomiasis in sub-Saharan Africa. Over recent years a raft of molecular tools have been developed enabling the genetic dissection of many aspects of trypanosome biology, including the mechanisms u...

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Detalles Bibliográficos
Autores principales: ALSFORD, SAM, KELLY, JOHN M., BAKER, NICOLA, HORN, DAVID
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759293/
https://www.ncbi.nlm.nih.gov/pubmed/23552488
http://dx.doi.org/10.1017/S003118201300022X
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author ALSFORD, SAM
KELLY, JOHN M.
BAKER, NICOLA
HORN, DAVID
author_facet ALSFORD, SAM
KELLY, JOHN M.
BAKER, NICOLA
HORN, DAVID
author_sort ALSFORD, SAM
collection PubMed
description The trypanosomes cause two neglected tropical diseases, Chagas disease in the Americas and African trypanosomiasis in sub-Saharan Africa. Over recent years a raft of molecular tools have been developed enabling the genetic dissection of many aspects of trypanosome biology, including the mechanisms underlying resistance to some of the current clinical and veterinary drugs. This has led to the identification and characterization of key resistance determinants, including transporters for the anti-Trypanosoma brucei drugs, melarsoprol, pentamidine and eflornithine, and the activator of nifurtimox-benznidazole, the anti-Trypanosoma cruzi drugs. More recently, advances in sequencing technology, combined with the development of RNA interference libraries in the clinically relevant bloodstream form of T. brucei have led to an exponential increase in the number of proteins known to interact either directly or indirectly with the anti-trypanosomal drugs. In this review, we discuss these findings and the technological developments that are set to further revolutionise our understanding of drug-trypanosome interactions. The new knowledge gained should inform the development of novel interventions against the devastating diseases caused by these parasites.
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spelling pubmed-37592932013-09-03 Genetic dissection of drug resistance in trypanosomes ALSFORD, SAM KELLY, JOHN M. BAKER, NICOLA HORN, DAVID Parasitology Research Article The trypanosomes cause two neglected tropical diseases, Chagas disease in the Americas and African trypanosomiasis in sub-Saharan Africa. Over recent years a raft of molecular tools have been developed enabling the genetic dissection of many aspects of trypanosome biology, including the mechanisms underlying resistance to some of the current clinical and veterinary drugs. This has led to the identification and characterization of key resistance determinants, including transporters for the anti-Trypanosoma brucei drugs, melarsoprol, pentamidine and eflornithine, and the activator of nifurtimox-benznidazole, the anti-Trypanosoma cruzi drugs. More recently, advances in sequencing technology, combined with the development of RNA interference libraries in the clinically relevant bloodstream form of T. brucei have led to an exponential increase in the number of proteins known to interact either directly or indirectly with the anti-trypanosomal drugs. In this review, we discuss these findings and the technological developments that are set to further revolutionise our understanding of drug-trypanosome interactions. The new knowledge gained should inform the development of novel interventions against the devastating diseases caused by these parasites. Cambridge University Press 2013-10 2013-04-03 /pmc/articles/PMC3759293/ /pubmed/23552488 http://dx.doi.org/10.1017/S003118201300022X Text en © Cambridge University Press 2013 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/3.0/>. The written permission of Cambridge University Press must be obtained for commercial re-use.
spellingShingle Research Article
ALSFORD, SAM
KELLY, JOHN M.
BAKER, NICOLA
HORN, DAVID
Genetic dissection of drug resistance in trypanosomes
title Genetic dissection of drug resistance in trypanosomes
title_full Genetic dissection of drug resistance in trypanosomes
title_fullStr Genetic dissection of drug resistance in trypanosomes
title_full_unstemmed Genetic dissection of drug resistance in trypanosomes
title_short Genetic dissection of drug resistance in trypanosomes
title_sort genetic dissection of drug resistance in trypanosomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759293/
https://www.ncbi.nlm.nih.gov/pubmed/23552488
http://dx.doi.org/10.1017/S003118201300022X
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