Trypanothione Reductase Gene Mutations in Meglumine Antimoniate Resistant Isolates from Cutaneous Leishmaniasis Patients Using Molecular Dynamics Method

In this study, mutations in the tripanothion reductase of isolated from Iran was investigated using sequencing and simulation of the enzyme by the molecular dynamic method. Fifteen susceptible and 15 clinical resistant specimens were collected from skin lesions from different regions of Iran in 2017. After DNA extraction, trypanothione reductase ( or ), 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. Some structural mutations were observed in 9 amino acids surrounding the active site of the gene of with three-dimensional trypanothione reductase alteration. Change in the active site of of , could probably contribute to the development of resistant to glucantime. Because of the likely occurrence of mutations in glucantime as well as the ease of development of 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.