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Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates

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...

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Autores principales: Kazemi-Rad, Elham, Mohebali, Mehdi, Khadem-Erfan, Mohammad Bagher, Hajjaran, Homa, Hadighi, Ramtin, Khamesipour, Ali, Rezaie, Sassan, Saffari, Mojtaba, Raoofian, Reza, Heidari, Mansour
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Parasitology and Tropical Medicine 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770871/
https://www.ncbi.nlm.nih.gov/pubmed/24039283
http://dx.doi.org/10.3347/kjp.2013.51.4.413
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author Kazemi-Rad, Elham
Mohebali, Mehdi
Khadem-Erfan, Mohammad Bagher
Hajjaran, Homa
Hadighi, Ramtin
Khamesipour, Ali
Rezaie, Sassan
Saffari, Mojtaba
Raoofian, Reza
Heidari, Mansour
author_facet Kazemi-Rad, Elham
Mohebali, Mehdi
Khadem-Erfan, Mohammad Bagher
Hajjaran, Homa
Hadighi, Ramtin
Khamesipour, Ali
Rezaie, Sassan
Saffari, Mojtaba
Raoofian, Reza
Heidari, Mansour
author_sort Kazemi-Rad, Elham
collection PubMed
description 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®) 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 a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance.
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spelling pubmed-37708712013-09-13 Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates Kazemi-Rad, Elham Mohebali, Mehdi Khadem-Erfan, Mohammad Bagher Hajjaran, Homa Hadighi, Ramtin Khamesipour, Ali Rezaie, Sassan Saffari, Mojtaba Raoofian, Reza Heidari, Mansour Korean J Parasitol Original Article 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®) 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 a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance. The Korean Society for Parasitology and Tropical Medicine 2013-08 2013-08-30 /pmc/articles/PMC3770871/ /pubmed/24039283 http://dx.doi.org/10.3347/kjp.2013.51.4.413 Text en © 2013, Korean Society for Parasitology and Tropical Medicine http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kazemi-Rad, Elham
Mohebali, Mehdi
Khadem-Erfan, Mohammad Bagher
Hajjaran, Homa
Hadighi, Ramtin
Khamesipour, Ali
Rezaie, Sassan
Saffari, Mojtaba
Raoofian, Reza
Heidari, Mansour
Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates
title Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates
title_full Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates
title_fullStr Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates
title_full_unstemmed Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates
title_short Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates
title_sort overexpression of ubiquitin and amino acid permease genes in association with antimony resistance in leishmania tropica field isolates
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770871/
https://www.ncbi.nlm.nih.gov/pubmed/24039283
http://dx.doi.org/10.3347/kjp.2013.51.4.413
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