Iranian Journal of Parasitology 2013. 8(3):359-366.

Downregulation of Calcineurin Gene Is Associated with Glucantime(®) Resiatance in Leishmania infantum.
Mohammad Bagher Khadem Erfan, Mehdi Mohebali, Elham Kazemi-Rad, Homa Hajjaran, Gholamhossein Edrissian, Setareh Mamishi, Mojtaba Saffari, Reza Raoofian, Mansour Heidari



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.

Conclusion: 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.


Antimonial resistance; Calcineurin gene; Leishmania infantum; Real-time RT-PCR; cDNA-AFLP

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