Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response.

ABSTRACT: Amphotericin B is increasingly used in treatment of leishmaniasis. Here, fourteen independent lines of Leishmania mexicana and one L. infantum line were selected for resistance to either amphotericin B or the related polyene antimicrobial, nystatin. Sterol profiling revealed that, in each resistant line, the predominant wild-type sterol, ergosta-5,7,24-trienol, was replaced by other sterol intermediates. Broadly, two different profiles emerged among the resistant lines. Whole genome sequencing then showed that these distinct profiles were due either to mutations in the sterol methyl transferase (C24SMT) gene locus or the sterol C5 desaturase (C5DS) gene. In three lines an additional deletion of the miltefosine transporter gene was found. Differences in sensitivity to amphotericin B were ap

SUBMITTER: Alpizar-Sosa EA 

PROVIDER: S-EPMC9581426 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature