<i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization
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 <i>Entamo...
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| Main Authors: | , , , |
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| Format: | Book |
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MDPI AG,
2021-08-01T00:00:00Z.
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| Summary: | 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 <i>Entamoeba histolytica</i> to 2 µM of AF that was acquired by gradual exposure of the parasite to an increasing amount of the drug. AF-adapted <i>E. histolytica</i> 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 <i>E. histolytica</i> 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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| Item Description: | 10.3390/antiox10081240 2076-3921 |