Multiple mutations in heterogeneous miltefosine-resistant Leishmania major population as determined by whole genome sequencing

全基因组测序确定异质性米替福新耐药利什曼原虫种群存在多种突变

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作者:Adriano C Coelho, Sébastien Boisvert, Angana Mukherjee, Philippe Leprohon, Jacques Corbeil, Marc Ouellette

Background

Miltefosine (MF) is the first oral compound used in the chemotherapy against leishmaniasis. Since the mechanism of action of this drug and the targets of MF in Leishmania are unclear, we generated in a step-by-step manner Leishmania major promastigote mutants highly resistant to MF. Two of the mutants were submitted to a short-read whole genome sequencing for identifying potential genes associated with MF resistance.

Significance

Whole genome sequencing was used to pinpoint known and new resistance markers associated with MF resistance in the protozoan parasite Leishmania. The study also demonstrated the polyclonal nature of a resistant population with individual cells with varying susceptibilities and genotypes.

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