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Comparison of gene expression patterns among Leishmania braziliensis clinical isolates showing a different in vitro susceptibility to pentavalent antimony

Published online by Cambridge University Press:  03 August 2010

V. ADAUI ,
K. SCHNORBUSCH ,
M. ZIMIC ,
A. GUTIÉRREZ ,
S. DECUYPERE ,
M. VANAERSCHOT ,
S. DE DONCKER ,
I. MAES ,
A. LLANOS-CUENTAS  and
F. CHAPPUIS
...Show all authors
V. ADAUI
Affiliation:
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium
K. SCHNORBUSCH
Affiliation:
Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium Department of Biomedical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium
M. ZIMIC
Affiliation:
Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
A. GUTIÉRREZ
Affiliation:
Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
S. DECUYPERE
Affiliation:
Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium
M. VANAERSCHOT
Affiliation:
Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium Department of Biomedical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium
S. DE DONCKER
Affiliation:
Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium
I. MAES
Affiliation:
Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium
A. LLANOS-CUENTAS
Affiliation:
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
F. CHAPPUIS
Affiliation:
Hôpitaux Universitaires de Genève, Department of Community Medicine, Geneva, Switzerland
J. ARÉVALO
Affiliation:
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
J.-C. DUJARDIN*
Affiliation:
Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium Department of Biomedical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium
*
*Corresponding author: Institute of Tropical Medicine, Unit of Molecular Parasitology, Nationalestraat 155, Antwerp B-2000, Belgium. Tel: +32 3 2476355. Fax: +32 3 2476359. E-mail: jcdujardin@itg.be
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Summary

Introduction. Evaluation of Leishmania drug susceptibility depends on in vitro SbV susceptibility assays, which are labour-intensive and may give a biased view of the true parasite resistance. Molecular markers are urgently needed to improve and simplify the monitoring of SbV-resistance. We analysed here the gene expression profile of 21 L. braziliensis clinical isolates in vitro defined as SbV-resistant and -sensitive, in order to identify potential resistance markers. Methods. The differential expression of 13 genes involved in SbV metabolism, oxidative stress or housekeeping functions was analysed during in vitro promastigote growth. Results. Expression profiles were up-regulated for 5 genes only, each time affecting a different set of isolates (mosaic picture of gene expression). Two genes, ODC (ornithine decarboxylase) and TRYR (trypanothione reductase), showed a significantly higher expression rate in the group of SbV-resistant compared to the group of SbV-sensitive parasites (P<0·01). However, analysis of individual isolates showed both markers to explain only partially the drug resistance. Discussion. Our results might be explained by (i) the occurrence of a pleiotropic molecular mechanism leading to the in vitro SbV resistance and/or (ii) the existence of different epi-phenotypes not revealed by the in vitro SbV susceptibility assays, but interfering with the gene expression patterns.

Keywords

Leishmania (Viannia) braziliensisantimony resistancegene expression profilingpromastigotesclinical isolates
Type
Research Article
Information
Parasitology , Volume 138 , Issue 2 , February 2011 , pp. 183 - 193
Copyright
Copyright © Cambridge University Press 2010

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