Increased copy number of the target gene squalene monooxygenase as the main resistance mechanism to terbinafine in Leishmania infantum.

ABSTRACT: We use here two genomic screens in an attempt to understand the mode of action and resistance mechanism of terbinafine, an antifungal contemplated as a potential drug against the parasite Leishmania. One screen consisted in in vitro drug evolution where 5 independent mutants were selected step-by-step for terbinafine resistance. Sequencing of the genome of the 5 mutants revealed no single nucleotide polymorphisms related to the resistance phenotype. However, the ERG1 gene was found amplified as part of a linear amplicon, and transfection of ERG1 fully recapitulated the terbinafine resistance phenotype of the mutants. The second screen, Cos-seq, consisted in selecting a gene overexpression library with terbinafine followed by the sequencing of the enriched cosmids. This screen identified tw

SUBMITTER: Potvin JE 

PROVIDER: S-EPMC10502319 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature