<i>Entamoeba histolytica</i> "mutator" strain with a high rate of genetic mutations assists the elucidation of drug resistance mechanisms.

ABSTRACT: In drug discovery, target identification and elucidation of resistance mechanisms are essential. The pathogen strains resistant to a compound of interest are useful for these purposes. As the generation of drug-resistant strains is time-consuming and often burdensome, we generated the Entamoeba histolytica strain with a high accumulation rate of genetic mutations by introducing proofreading-deficient, error-prone DNA polymerase δ mutant gene under the regulation of a tetracycline-regulatable promoter. We validated this "mutator" strain by showing higher genetic mutations accumulated during in vitro passage and, as a proof of concept, by identifying genes and their mutations responsible for resistance against miltefosine. Whole-genome analyses of the mutator strain after 12, 3

SUBMITTER: Saito-Nakano Y 

PROVIDER: S-EPMC12323330 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature