An Alcohol Dehydrogenase 3 (ADH3) from Entamoeba histolytica Is Involved in the Detoxification of Toxic Aldehydes

König, Constantin; Meyer, Martin; Lender, Corinna; Nehls, Sarah; Wallaschkowski, Tina; Holm, Tobias; Matthies, Thorben; Lercher, Dirk; Matthiesen, Jenny; Fehling, Helena; Roeder, Thomas; Reindl, Sophia; Rosenthal, Maria; Metwally, Nahla Galal; Lotter, Hannelore; Bruchhaus, Iris

doi:10.3390/microorganisms8101608

Cited by 6 publications

(6 citation statements)

References 38 publications

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“…However, we did recover a glycyl-radical enzyme-activating enzyme (GRE-AE) highly similar to PFL-AE that was previously documented in Giardia [ 12 ], and later Entamoeba and Trichomonas [ 99 ]; we additionally find it in other Archamoebae and anaerobic members of SAR ( Fig 4A ). We expand the taxonomic scope of other previously-reported GFs, such as the alcohol dehydrogenase EhADH3B originally reported as an LTG unique to the human parasite Entamoeba histolytica [ 100 ] where it is associated with pathogenicity [ 101 ]; we recovered this GF in other Archamoebae, Trichomonas , and Blastocystis . Similarly, we find the nitroreductase Fd-NR2 in Entamoeba , expanding its presence from a previous report as an LTG only in Giardia [ 102 ] ( S3 Table ).…”

Section: Resultsmentioning

confidence: 69%

Old genes in new places: A taxon-rich analysis of interdomain lateral gene transfer events

Cote-L'Heureux

Maurer‐Alcalá²,

Katz³

2022

PLoS Genet

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Vertical inheritance is foundational to Darwinian evolution, but fails to explain major innovations such as the rapid spread of antibiotic resistance among bacteria and the origin of photosynthesis in eukaryotes. While lateral gene transfer (LGT) is recognized as an evolutionary force in prokaryotes, the role of LGT in eukaryotic evolution is less clear. With the exception of the transfer of genes from organelles to the nucleus, a process termed endosymbiotic gene transfer (EGT), the extent of interdomain transfer from prokaryotes to eukaryotes is highly debated. A common critique of studies of interdomain LGT is the reliance on the topology of single-gene trees that attempt to estimate more than one billion years of evolution. We take a more conservative approach by identifying cases in which a single clade of eukaryotes is found in an otherwise prokaryotic gene tree (i.e. exclusive presence). Starting with a taxon-rich dataset of over 13,600 gene families and passing data through several rounds of curation, we identify and categorize the function of 306 interdomain LGT events into diverse eukaryotes, including 189 putative EGTs, 52 LGTs into Opisthokonta (i.e. animals, fungi and their microbial relatives), and 42 LGTs nearly exclusive to anaerobic eukaryotes. To assess differential gene loss as an explanation for exclusive presence, we compare branch lengths within each LGT tree to a set of vertically-inherited genes subsampled to mimic gene loss (i.e. with the same taxonomic sampling) and consistently find shorter relative distance between eukaryotes and prokaryotes in LGT trees, a pattern inconsistent with gene loss. Our methods provide a framework for future studies of interdomain LGT and move the field closer to an understanding of how best to model the evolutionary history of eukaryotes.

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Section: Resultsmentioning

confidence: 69%

Old genes in new places: A taxon-rich analysis of interdomain lateral gene transfer events

Cote-L'Heureux

Maurer‐Alcalá²,

Katz³

2022

PLoS Genet

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“…Pyruvate:ferredoxin oxidoreductase (EHI_051060), NADP-dependent alcohol dehydrogenase (EHI_107210), and Fe-ADH domain-containing protein (EHI_198760), which encode for proteins involved in redox regulation: These redox enzymes depend on cysteine residues for their activity [ 47 , 48 , 49 ]. The oxidation of these cysteine residues impairs their activity [ 47 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Entamoeba histolytica Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization

et al. 2021

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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 Entamoeba histolytica to 2 µM of AF that was acquired by gradual exposure of the parasite to an increasing amount of the drug. AF-adapted E. histolytica 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 E. histolytica 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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“…Pyruvate:ferredoxin oxidoreductase (EHI_051060), NADP-dependent alcohol dehydrogenase (EHI_107210) and Fe-ADH domain-containing protein (EHI_198760) which encode for proteins involved in redox regulation. These redox enzymes depend on cysteine residues for their activity [48–50]. The oxidation of these cysteine residues impairs their activity [48,51].…”

Section: Discussionmentioning

confidence: 99%

Entamoeba histolytica adaption to auranofin: a phenotypic and multi-omics characterization

Shaulov

Sarid

Trebicz-Geffen

et al. 2021

Preprint

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Auranofin (AF), an antirheumatic agent, targets mammalian thioredoxin reductase (TrxR), an important enzyme controlling redox homeostasisis, AF is also very effective against a diversity of pathogenic bacteria and protozoan parasites. Here, we report about the resistance of the parasite Entamoeba histolytica to 2 microM of AF that has been acquired by gradual exposure of the parasite to increasing amount of the drug. AF adapted E.histolytica trophozoites (AFAT) has an impaired growth, cytopathic activity and they are more sensitive to oxidative stress (OS), nitrosative stress (NS) and metronidazole (MTZ) 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 of acute AF trophozoites. Overexpression of E.histolytica TrxR (EhTrxR) did not protect the parasite against AF which suggests that EhTrxR is not central is the mechanism of adaptation to AF.

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An Alcohol Dehydrogenase 3 (ADH3) from Entamoeba histolytica Is Involved in the Detoxification of Toxic Aldehydes

Cited by 6 publications

References 38 publications

Old genes in new places: A taxon-rich analysis of interdomain lateral gene transfer events

Old genes in new places: A taxon-rich analysis of interdomain lateral gene transfer events

Entamoeba histolytica Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization

Entamoeba histolytica adaption to auranofin: a phenotypic and multi-omics characterization

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