Role of Mutation in Sb (V)-As (V) Reductase Enzyme of Leishmania tropica Isolates Resistant to Glucantim in Iran

 Glucantime has been considered as a drug of choice for treating cutaneous leishmaniasis for many years. In the recent years, resistance to Glucantime has been increasingly reported in some regions of Iran. In the Leishmania, Arsenate/Antimony reductase acts on the basis of thiol metabolism; it can donate the electron from reduced glutaredoxin to pentavalent (sbV) antimony and arsenate and reduce them to trivalent (sbIII) antimony and arsenite, based on its enzymatic property. It has been assumed that a functional mutation in the enzyme can result in drug resistance. In the present study, the role of Sb (V)-As (V) reductase of Leishmania tropica in drug resistant to glucantime was investigated.

 In the present experimental research, 15 glucantime sensitive samples and 15 glucantime resistant specimens were collected from different regions of Iran through patients with cutaneous leishmaniasis. For mutation detection, first degenerate primers were designed; then, sequencing and simulation techniques were used based on molecular dynamics method.

In Leishmania tropica-resistant isolates, only one mutation was seen as replacing alanine (Ala) at position 80 instead of valine (Val). The analysis of the radius of gyration did not reveal any increase in the radius of gyration while simulation.

Mutations in glucantime-resistant isolates did not significantly change simulated active site of antimony ion.