Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains
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 involv...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | International Journal of Microbiology |
| Online Access: | http://dx.doi.org/10.1155/2010/819060 |
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| author | C. Mary F. Faraut M. Deniau J. Dereure K. Aoun S. Ranque R. Piarroux |
| author_facet | C. Mary F. Faraut M. Deniau J. Dereure K. Aoun S. Ranque R. Piarroux |
| author_sort | C. Mary |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9f57752d93204df9a785bd721653792f |
| institution | Kabale University |
| issn | 1687-918X 1687-9198 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Microbiology |
| spelling | doaj-art-9f57752d93204df9a785bd721653792f2025-02-03T06:43:47ZengWileyInternational Journal of Microbiology1687-918X1687-91982010-01-01201010.1155/2010/819060819060Frequency of Drug Resistance Gene Amplification in Clinical Leishmania StrainsC. Mary0F. Faraut1M. Deniau2J. Dereure3K. Aoun4S. Ranque5R. Piarroux6Laboratoire de Parasitologie-Mycologie, Hôpital de la Timone, 264 Rue Saint Pierre, 13385 Marseille cedex 5, FranceLaboratoire de Parasitologie-Mycologie, Hôpital de la Timone, 264 Rue Saint Pierre, 13385 Marseille cedex 5, FranceUMR 956, UPVM, Hôpital Henri Mondor, 94010 Créteil, FranceLaboratoire de Parasitologie-Mycologie 163, Rue Auguste Broussonet, 34090 Montpellier, FranceInstitut Pasteur de Tunis, Place Pasteur B.P. 74 Tunis Belvédère, Tunisie 1002, TunisiaLaboratoire de Parasitologie-Mycologie, Hôpital de la Timone, 264 Rue Saint Pierre, 13385 Marseille cedex 5, FranceLaboratoire de Parasitologie-Mycologie, Hôpital de la Timone, 264 Rue Saint Pierre, 13385 Marseille cedex 5, FranceExperimental 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.http://dx.doi.org/10.1155/2010/819060 |
| spellingShingle | C. Mary F. Faraut M. Deniau J. Dereure K. Aoun S. Ranque R. Piarroux Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains International Journal of Microbiology |
| title | Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains |
| title_full | Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains |
| title_fullStr | Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains |
| title_full_unstemmed | Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains |
| title_short | Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains |
| title_sort | frequency of drug resistance gene amplification in clinical leishmania strains |
| url | http://dx.doi.org/10.1155/2010/819060 |
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