Downregulation of calcineurin gene is associated with glucan-time[registered sign] resiatance in leishmania infantum

ABSTRACT

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[registered sign] resiatance strain of L. infan-tum. 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. 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. This is the first report of calcineurin implication in Glucantime[registered sign] drug resistance of field [natural] isolate of L. infantum. Downregulation of calcineurin could protect parasites from antimonial-induced apoptosis