Identification of antimony resistance markers in Leishmania tropica field isolates through a cDNA-AFLP approach

Kazemi-Rad, E. and Mohebali, M. and Erfan, M.B.K. and Saffari, M. and Raoofian, R. and Hajjaran, H. and Hadighi, R. and Khamesipour, A. and Rezaie, S. and Abedkhojasteh, H. and Heidari, M. (2013) Identification of antimony resistance markers in Leishmania tropica field isolates through a cDNA-AFLP approach. Experimental Parasitology, 135 (2). pp. 344-349.

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Pentavalent antimonial compounds have been the first line therapy for leishmaniasis; unfortunately the rate of treatment failure of anthroponotic cutaneous leishmaniasis (ACL) is increasing due to emerging of drug resistance. Elucidation of the molecular mechanisms operating in antimony resistance is critical for development of new strategies for treatment. Here, we used a cDNA-AFLP approach to identify gene(s) which are differentially expressed in resistant and sensitive Leishmania tropica field isolates. We identified five genes, aquaglyceroporin (AQP1) acts in drug uptake, ATP-binding cassette (ABC) transporter (MRPA) involved in sequestration of drug, phosphoglycerate kinase (PGK) implicated in glycolysis metabolism, mitogen activated protein kinase (MAPK) and protein tyrosine phosphatase (PTP) responsible for phosphorylation pathway. The results were confirmed using real time RT-PCR which revealed an upregulation of MRPA, PTP and PGK genes and downregulation of AQP1 and MAPK genes in resistant isolate. To our knowledge, this is the first report of identification of PTP and PGK genes potentially implicated in resistance to antimonials. Our findings support the idea that distinct biomolecules might be involved in antimony resistance in L. tropica field isolates. © 2013 Elsevier Inc.

Item Type: Article
Additional Information: cited By 36
Uncontrolled Keywords: ABC transporter; meglumine antimonate; mitogen activated protein kinase; protein tyrosine phosphatase, amplified fragment length polymorphism; antimalarial drug resistance; antimalarial drug susceptibility; aquaglyceroporin 1 gene; article; ATP binding cassette transporter gene; cDNA amplified fragment length polymorphism; controlled study; down regulation; gene expression; Leishmania tropica; mitogen activated protein kinase gene; nonhuman; phosphoglycerate kinase B gene; priority journal; protein tyrosine phosphatase gene; real time polymerase chain reaction; reverse transcription polymerase chain reaction; upregulation, Antimony resistance; cDNA-AFLP; Leishmania tropica; Real-time RT-PCR, Amplified Fragment Length Polymorphism Analysis; Antimony; Antiprotozoal Agents; Cell Line; DNA Fragmentation; DNA, Complementary; DNA, Protozoan; Drug Resistance; Genes, Protozoan; Inhibitory Concentration 50; Leishmania tropica; Meglumine; Organometallic Compounds; Parasitic Sensitivity Tests; Real-Time Polymerase Chain Reaction; RNA, Protozoan
Subjects: WC Communicable Diseases
Depositing User: somayeh pourmorteza
Date Deposited: 26 May 2019 06:30
Last Modified: 26 May 2019 06:30

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