Delving in folate metabolism in the parasite Leishmania major through a chemogenomic screen and methotrexate selection.

ABSTRACT: Most of our understanding of folate metabolism in the parasite Leishmania is derived from studies of resistance to the antifolate methotrexate (MTX). A chemical mutagenesis screen of L. major Friedlin and selection for resistance to MTX led to twenty mutants with a 2- to 400-fold decrease in MTX susceptibility in comparison to wild-type cells. The genome sequence of the twenty mutants highlighted recurrent mutations (SNPs, gene deletion) in genes known to be involved in folate metabolism but also in novel genes. The most frequent events occurred at the level of the locus coding for the folate transporter FT1 and included gene deletion and gene conversion events, as well as single nucleotide changes. The role of some of these FT1 point mutations in MTX resistance was validated by gene editi

SUBMITTER: Bigot S 

PROVIDER: S-EPMC10337921 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature