Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization

Overview

Journal Antioxidants (Basel)

Date 2021 Aug 27

PMID 34439488

Citations 8

Authors

Yana Shaulov

Lotem Sarid

Meirav Trebicz-Geffen

Serge Ankri

Affiliations

Soon will be listed here.

Abstract

Auranofin (AF), an antirheumatic agent, targets mammalian thioredoxin reductase (TrxR), an important enzyme controlling redox homeostasis. AF is also highly effective against a diversity of pathogenic bacteria and protozoan parasites. Here, we report on the resistance of the parasite to 2 µM of AF that was acquired by gradual exposure of the parasite to an increasing amount of the drug. AF-adapted trophozoites (AFAT) have impaired growth and cytopathic activity, and are more sensitive to oxidative stress (OS), nitrosative stress (NS), and metronidazole (MNZ) than wild type (WT) trophozoites. Integrated transcriptomics and redoxomics analyses showed that many upregulated genes in AFAT, including genes encoding for dehydrogenase and cytoskeletal proteins, have their product oxidized in wild type trophozoites exposed to AF (acute AF trophozoites) but not in AFAT. We also showed that the level of reactive oxygen species (ROS) and oxidized proteins (OXs) in AFAT is lower than that in acute AF trophozoites. Overexpression of TrxR (EhTrxR) did not protect the parasite against AF, which suggests that EhTrxR is not central to the mechanism of adaptation to AF.

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