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International Journal of Microbiology
Volume 2010 (2010), Article ID 819060, 8 pages
Research Article

Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains

1Laboratoire de Parasitologie-Mycologie, Hôpital de la Timone, 264 Rue Saint Pierre, 13385 Marseille cedex 5, France
2UMR 956, UPVM, Hôpital Henri Mondor, 94010 Créteil, France
3Laboratoire de Parasitologie-Mycologie 163, Rue Auguste Broussonet, 34090 Montpellier, France
4Institut Pasteur de Tunis, Place Pasteur B.P. 74 Tunis Belvédère, Tunisie 1002, Tunisia

Received 18 January 2010; Revised 4 June 2010; Accepted 13 June 2010

Academic Editor: Isabel Sá-Correia

Copyright © 2010 C. Mary et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Experimental studies about Leishmania resistance to metal and antifolates have pointed out that gene amplification is one of the main mechanisms of drug detoxification. Amplified genes code for adenosine triphosphate-dependent transporters (multidrug resistance and P-glycoproteins P), enzymes involved in trypanothione pathway, particularly gamma glutamyl cysteine synthase, and others involved in folates metabolism, such as dihydrofolate reductase and pterine reductase. The aim of this study was to detect and quantify the amplification of these genes in clinical strains of visceral leishmaniasis agents: Leishmania infantum, L. donovani, and L. archibaldi. Relative quantification experiments by means of real-time polymerase chain reaction showed that multidrug resistance gene amplification is the more frequent event. For P-glycoproteins P and dihydrofolate reductase genes, level of amplification was comparable to the level observed after in vitro selection of resistant clones. Gene amplification is therefore a common phenomenon in wild strains concurring to Leishmania genomic plasticity. This finding, which corroborates results of experimental studies, supports a better understanding of metal resistance selection and spreading in endemic areas.