Iranian Journal of Parasitology (Sep 2013)
Downregulation of Calcineurin Gene is Associated with Glucantime Resiatance in Leishmania Infantum
Abstract
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. Calcineurin 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. infantum.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 resistant isolate in comparison with susceptible one. Significant downregulation of calcineurin (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.