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

ABSTRACT:

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.

Methods/principal findings

Analysis of the genome assemblies revealed several independent point mutations in a P-type ATPase involved in phospholipid translocation. Mutations in two other proteins-pyridoxal kinase and α-adaptin like protein-were also observed in independent mutants. The role of these proteins in the MF resistance was evaluated by gene

SUBMITTER: Coelho AC 

PROVIDER: S-EPMC3279362 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature