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Identification of a Leishmania infantum gene mediating resistance to miltefosine and SbIII

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50397

Kube,  Michael
High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50488

Reinhardt,  Richard
High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Choudhurya, K., Zander, D., Kube, M., Reinhardt, R., & Clos, J. (2008). Identification of a Leishmania infantum gene mediating resistance to miltefosine and SbIII. International Journal for Parasitology, 38(12), 1411-1423. doi:10.1016/j.ijpara.2008.03.005.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-800E-F
Zusammenfassung
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 SbIII, 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.