Simvastatin Resistance of Leishmania amazonensis Induces Sterol Remodeling and Cross-Resistance to Sterol Pathway and Serine Protease Inhibitors.

ABSTRACT: The sterol biosynthesis pathway of Leishmania spp. is used as a pharmacological target; however, available information about the mechanisms of the regulation and remodeling of sterol-related genes is scarce. The present study investigated compensatory mechanisms of the sterol biosynthesis pathway using an inhibitor of HMG-CoA reductase (simvastatin) and by developing drug-resistant parasites to evaluate the impact on sterol remodeling, cross-resistance, and gene expression. Simvastatin-resistant L. amazonensis parasites (LaSimR) underwent reprogramming of sterol metabolism manifested as an increase in cholestane- and stigmastane-based sterols and a decrease in ergostane-based sterols. The levels of the transcripts of sterol 24-C-methyltransferase (SMT), sterol C14-α-demethylase (C14DM), an

SUBMITTER: Fujii TTS 

PROVIDER: S-EPMC8877030 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature