In Vitro Selection Implicates ROP1 as a Resistance Gene for an Experimental Therapeutic Benzoquinone Acyl Hydrazone in Toxoplasma gondii.

ABSTRACT: Toxoplasma gondii is a globally distributed apicomplexan parasite and the causative agent of toxoplasmosis in humans. While pharmaceuticals exist to combat acute infection, they can produce serious adverse reactions, demonstrating a need for enhanced therapies. KG8 is a benzoquinone acyl hydrazone chemotype identified from a previous chemical screen for which we previously showed in vitro and in vivo efficacy against T. gondii However, the genetic target and mechanism of action of KG8 remain unknown. To investigate potential targets, we generated resistant T. gondii lines by chemical mutagenesis followed by in vitro selection. Whole-genome sequencing of resistant clones revealed a P207S mutation in the gene encoding rhoptry organelle protein 1 (ROP

SUBMITTER: Martens MC 

PROVIDER: S-EPMC8092512 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature