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(Post-) Genomic approaches to tackle drug resistance in Leishmania

Published online by Cambridge University Press:  12 March 2013

MAYA BERG ,
AN MANNAERT ,
MANU VANAERSCHOT ,
GERT VAN DER AUWERA  and
JEAN-CLAUDE DUJARDIN
MAYA BERG
Affiliation:
Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium
AN MANNAERT
Affiliation:
Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium
MANU VANAERSCHOT
Affiliation:
Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium
GERT VAN DER AUWERA
Affiliation:
Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium
JEAN-CLAUDE DUJARDIN*
Affiliation:
Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
*
*Corresponding author. Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat, 155; B-2000 Antwerpen, Belgium. Tel: 32.3.2476355. Fax: +32.3.2476359. E-mail: jcdujardin@itg.be
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Summary

Leishmaniasis, like other neglected diseases is characterized by a small arsenal of drugs for its control. To safeguard the efficacy of current drugs and guide the development of new ones it is thus of utmost importance to acquire a deep understanding of the phenomenon of drug resistance and its link with treatment outcome. We discuss here how (post-)genomic approaches may contribute to this purpose. We highlight the need for a clear definition of the phenotypes under consideration: innate and acquired resistance versus treatment failure. We provide a recent update of our knowledge on the Leishmania genome structure and dynamics, and compare the contribution of targeted and untargeted methods for the understanding of drug resistance and show their limits. We also present the main assays allowing the experimental validation of the genes putatively involved in drug resistance. The importance of analysing information downstream of the genome is stressed and further illustrated by recent metabolomics findings. Finally, the attention is called onto the challenges for implementing the acquired knowledge to the benefit of the patients and the population at risk.

Keywords

Leishmaniadrug resistanceantimonialsmiltefosinegenomicsmetabolomics
Type
Research Article
Information
Parasitology , Volume 140 , Issue 12: Genetic and genomic approaches to understanding drug resistance in parasites , October 2013 , pp. 1492 - 1505
Copyright
Copyright © Cambridge University Press 2013 

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