Trypanothione Reductase Gene Mutations in Meglumine Anti-moniate Resistant Isolates from Cutaneous Leishmaniasis Pa-tients Using Molecular Dynamics Method

Abstract

Background: In this study, mutations in the tripanothion reductase of Leishmania tropica isolated from Iran was investigated using sequencing and simulation of the enzyme by the molecular dynamic method.
 Methods: Fifteen susceptible and 15 clinical resistant L. tropica specimens were collected from skin lesions from different regions of Iran in 2017. After DNA extraction, trypanothione reductase (TRYR or TPR), gene fragment was amplified using PCR and sequencing methods. In the case of structural mutations, the components were simulated by molecular dynamics using the GROMACS software.
 Results: Some structural mutations were observed in 9 amino acids surrounding the active site of the TRYR gene of L. tropica with three-dimensional trypanothione reductase alteration.
 Conclusion: Change in the active site of TRYR of L. tropica, could probably contribute to the development of resistant L. tropica to glucantime. Because of the likely occurrence of mutations in glucantime as well as the ease of development of L. tropica resistant populations, more samples are needed to demonstrate the relationship between mutations in this enzyme and clinical resistance to glucantime. On the other hand, it is recommended that enzymatic studies be performed to confirm the role of mutation in the function and expression of trypanothione reductase in glucantime resistant and susceptible populations.

Identification of the parasites that cause children's cutaneous leishmaniasis and several types of immune response cells

“…Therefore, molecular diagnostics was relied on in the current study, characterized by its diagnostic efficiency, quantity and accuracy. The high sensitivity of molecular methods has been confirmed 13,14 .…”