Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana.

ABSTRACT: Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance. Here we select amphotericin B-resistant Leishmania mexicana parasites with relative ease. Metabolomic analysis demonstrated that ergosterol, the sterol known to bind the drug, is prevalent in wild-type cells, but diminished in the resistant line, where alternative sterols become prevalent. This indicates that the resistance phenotype is related to loss of drug binding. Comparing sequences of the parasites' genomes revealed a plethora of single nucleotide polymorphisms t

SUBMITTER: Mwenechanya R 

PROVIDER: S-EPMC5498063 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature