<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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/8/1240 |
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| author | Yana Shaulov Lotem Sarid Meirav Trebicz-Geffen Serge Ankri |
| author_facet | Yana Shaulov Lotem Sarid Meirav Trebicz-Geffen Serge Ankri |
| author_sort | Yana Shaulov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T09:03:41Z |
| format | Article |
| id | doaj.art-cb11452b82044f20b7d4c15f329c40d0 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T09:03:41Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-cb11452b82044f20b7d4c15f329c40d02023-11-22T06:36:11ZengMDPI AGAntioxidants2076-39212021-08-01108124010.3390/antiox10081240<i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics CharacterizationYana Shaulov0Lotem Sarid1Meirav Trebicz-Geffen2Serge Ankri3Department of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, 31096 Haifa, IsraelDepartment of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, 31096 Haifa, IsraelDepartment of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, 31096 Haifa, IsraelDepartment of Molecular Microbiology, Ruth and Bruce Rappaport Faculty of Medicine, Technion, 31096 Haifa, IsraelAuranofin (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.https://www.mdpi.com/2076-3921/10/8/1240<i>Entamoeba histolytica</i>auranofindrug resistancetranscriptomicsredoxomicsthioredoxin reductase |
| spellingShingle | Yana Shaulov Lotem Sarid Meirav Trebicz-Geffen Serge Ankri <i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization Antioxidants <i>Entamoeba histolytica</i> auranofin drug resistance transcriptomics redoxomics thioredoxin reductase |
| title | <i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization |
| title_full | <i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization |
| title_fullStr | <i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization |
| title_full_unstemmed | <i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization |
| title_short | <i>Entamoeba histolytica</i> Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization |
| title_sort | i entamoeba histolytica i adaption to auranofin a phenotypic and multi omics characterization |
| topic | <i>Entamoeba histolytica</i> auranofin drug resistance transcriptomics redoxomics thioredoxin reductase |
| url | https://www.mdpi.com/2076-3921/10/8/1240 |
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