Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum.
BACKGROUND
Pentavalent antimonials are the first line drugs for the treatment of leishmaniasis. Unresponsiveness of Leishmania spp. to antimonial drugs is a serious problem in some endemic areas. Investigations on molecular mechanisms involved in drug resistance are essential for monitoring and managing of the disease. Cal-cineurin is an essential protein phosphatase for number of signal transduction pathways in eukaryotic cells and it has a mediated role in apoptosis. This study aimed to determine of biomarker(s) in Glucantime(®) resiatance strain of L. infan-tum.


METHODS
We used cDNA amplified fragment length polymorphism (cDNA-AFLP) and real time-RT PCR assays to compare gene expression profiles at the mRNA levels in resistant and susceptible L. infantum field isolates.


RESULTS
The cDNA-AFLP results showed downlegulation of calcineurin in resis-tant isolate in comparison with susceptible one. Significant downregulation of cal-cineurin (0.42 fold) (P<0.05) was found in resistant isolate compared to susceptible one by Real time-RT PCR.


CONCLUSIONS
This is the first report of calcineurin implication in Glucantime(®) drug resistance of field (natural) isolate of L. infantum. Downregulation of calcineurin could protect parasites from antimonial-induced apoptosis.
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad
M
Bagher Khadem Erfan
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran ; Center for Research of Endemic Parasites of Iran (CREPI), Tehran University of Medical Sciences, Tehran, Iran.
Mehdi
M
Mohebali
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Elham
E
Kazemi-Rad
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Homa
H
Hajjaran
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Gholamhossein
G
Edrissian
Pediatric Infectious Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Setareh
S
Mamishi
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
Mojtaba
M
Saffari
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
Reza
R
Raoofian
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran ; Stem Cell Preparation Unit, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Mansour
M
Heidari
Antimonial resistance; Calcineurin gene; Leishmania infantum; Real-time RT-PCR; cDNA-AFLP