A protein of the leucine-rich repeats (LRRs) superfamily is implicated in antimony resistance in Leishmania infantum amastigotes

Pentavalent antimonial containing drugs (SbV) are the mainstay for the control of the protozoan parasite Leishmania but resistance to this class of drug is now prevalent in several endemic areas. We describe here the use of functional cloning where an expression cosmid bank derived from Leishmania infantum was transfected in L. infantum axenic amastigotes and selected for potassium antimonyl tartrate (SbIII) resistance. This strategy allowed the isolation of a cosmid encoding for a novel resistance protein, LinJ34.0570, which belongs to the superfamily of leucine-rich repeat (LRR) proteins. Parasites overexpressing this LRR protein, which is part of the LRR_CC subfamily, were resistant to SbIII as axenic amastigotes and to SbV as intracellular parasites. This work pinpoints a novel protein that can contribute to antimonial resistance in Leishmania.