title: Identification of a Leishmania infantum gene mediating resistance to miltefosine and SbIII.
abstract: Resistance to treatment is a growing problem in efforts to control Old World leishmaniasis. Parasites resistant to new therapeutics such as miltefosine have not been reported from the field yet but based on experimental evidence, may appear soon. Therefore, we attempted to identify genetic markers that may correlate with miltefosine resistance. Using a functional cloning approach, we have isolated a gene from Leishmania infantum that, upon over-expression, confers protection not only against miltefosine, but also against Sb(III), the active principle of anti-leishmanial antimonials. The gene encodes a very large putative polypeptide of 299 kDa that shows no similarities to known proteins or functional motifs. Database mining and karyotyping experiments suggest that in L. infantum this gene is part of a 44-kbp duplicated region that is found on two separate chromosomes, CHR08 and CHR29.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, RG Leishmaniasis, Bernhard Nocht St 74, D-20359 Hamburg, Germany.
authors.forename: Kohelia
authors.initials: K
authors.lastname: Choudhury
authors.forename: Dorothea
authors.initials: D
authors.lastname: Zander
authors.forename: Michael
authors.initials: M
authors.lastname: Kube
authors.forename: Richard
authors.initials: R
authors.lastname: Reinhardt
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
mesh_terms: D000818:Animals; D000966:Antimony Potassium Tartrate; D003360:Cosmids / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D018314:Leishmania infantum / Q000235:genetics* / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000235:genetics*; D010767:Phosphorylcholine / Q000031:analogs & derivatives*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015800:Protozoan Proteins; D010767:Phosphorylcholine; C039128:miltefosine; D000966:Antimony Potassium Tartrate