Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates

  • Kazemi-Rad, Elham (Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences) ;
  • Mohebali, Mehdi (Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences) ;
  • Erfan, Mohammad Bagher Khadem (Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences) ;
  • Hajjaran, Homa (Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences) ;
  • Hadighi, Ramtin (Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences) ;
  • Khamesipour, Ali (Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences) ;
  • Rezaie, Sassan (Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences) ;
  • Saffari, Mojtaba (Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences) ;
  • Raoofian, Reza (Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences) ;
  • Heidari, Mansour (Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences)
  • Received : 2013.02.05
  • Accepted : 2013.05.03
  • Published : 2013.08.31
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Abstract

The mainstay therapy against leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime$^{(R)}$) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in resistant isolates compared to sensitive ones. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance.

Keywords

References

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