Frequency of Drug Resistance Gene Amplification in ClinicalLeishmaniaStrains
Open Access
- 12 July 2010
- journal article
- research article
- Published by Hindawi Limited in International Journal of Microbiology
- Vol. 2010, 1-8
- https://doi.org/10.1155/2010/819060
Abstract
Experimental studies aboutLeishmaniaresistance 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, andL. 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 toLeishmaniagenomic plasticity. This finding, which corroborates results of experimental studies, supports a better understanding of metal resistance selection and spreading in endemic areas.Keywords
Funding Information
- Assistance Publique, Hopitaux de Marseille
This publication has 37 references indexed in Scilit:
- Leishmania major ascorbate peroxidase overexpression protects cells against reactive oxygen species-mediated cardiolipin oxidationFree Radical Biology & Medicine, 2008
- Alteration in glycerol and metalloid permeability by a single mutation in the extracellular C‐loop of Leishmania major aquaglyceroporin LmAQP1Molecular Microbiology, 2008
- Modulation of gene expression in drug resistant Leishmania is associated with gene amplification, gene deletion and chromosome aneuploidyGenome Biology, 2008
- Resistance ofLeishmania donovanito Sodium Stibogluconate Is Related to the Expression of Host and Parasite γ-Glutamylcysteine SynthetaseAntimicrobial Agents and Chemotherapy, 2006
- Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental modelsZeitschrift für Parasitenkunde, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Real-Time PCR as a New Tool for Quantifying Leishmania infantum in Liver in Infected MiceClinical and Diagnostic Laboratory Immunology, 2001
- Structural and Functional Analysis of theLaMDR1Multidrug Resistance Gene inLeishmania amazonensisBiochemical and Biophysical Research Communications, 1999
- Linear amplicons as precursors of amplified circles in methotrexate- resistant Leishmania tarentolaeNucleic Acids Research, 1998
- Mechanisms of drug resistance in LeishmaniaParasitology Today, 1993