{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:32:19Z","timestamp":1790256739752,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T00:00:00Z","timestamp":1603065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010127","name":"J\u00fcrgen Manchot Stiftung","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/100010127","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BR1744\/17-1"],"award-info":[{"award-number":["BR1744\/17-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Recently, a putative alcohol dehydrogenase 3, termed EhADH3B of the Entamoeba histolytica isolate HM-1:IMSS was identified, which is expressed at higher levels in non-pathogenic than in pathogenic amoebae and whose overexpression reduces the virulence of pathogenic amoebae. In an in silico analysis performed in this study, we assigned EhADH3B to a four-member ADH3 family, with ehadh3b present as a duplicate (ehadh3ba\/ehadh3bb). In long-term laboratory cultures a mutation was identified at position 496 of ehadh3ba, which codes for a stop codon, which was not the case for amoebae isolated from human stool samples. When using transfectants that overexpress or silence ehadh3bb, we found no or little effect on growth, size, erythrophagocytosis, motility, hemolytic or cysteine peptidase activity. Biochemical characterization of the recombinant EhADH3Bb revealed that this protein forms a dimer containing Ni2+ or Zn2+ as a co-factor and that the enzyme converts acetaldehyde and formaldehyde in the presence of NADPH. A catalytic activity based on alcohols as substrates was not detected. Based on the results, we postulate that EhADH3Bb can reduce free acetaldehyde released by hydrolysis from bifunctional acetaldehyde\/alcohol dehydrogenase-bound thiohemiacetal and that it is involved in detoxification of toxic aldehydes produced by the host or the gut microbiota.<\/jats:p>","DOI":"10.3390\/microorganisms8101608","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T09:36:28Z","timestamp":1603100188000},"page":"1608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An Alcohol Dehydrogenase 3 (ADH3) from Entamoeba histolytica Is Involved in the Detoxification of Toxic Aldehydes"],"prefix":"10.3390","volume":"8","author":[{"given":"Constantin","family":"K\u00f6nig","sequence":"first","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Meyer","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Lender","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Nehls","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Wallaschkowski","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Holm","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorben","family":"Matthies","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Lercher","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Matthiesen","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1112-7608","authenticated-orcid":false,"given":"Helena","family":"Fehling","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Roeder","sequence":"additional","affiliation":[{"name":"Molecular Physiology Department, Zoological Institute, Christian-Albrechts University Kiel, 24118 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Reindl","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-936X","authenticated-orcid":false,"given":"Maria","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9423-7145","authenticated-orcid":false,"given":"Nahla Galal","family":"Metwally","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannelore","family":"Lotter","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-7409","authenticated-orcid":false,"given":"Iris","family":"Bruchhaus","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2013 Mortality and Causes of Death Collaborators (2015). Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990\u20132013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet, 385, 117\u2013171.","DOI":"10.1016\/S0140-6736(14)61682-2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0065-308X(08)60286-9","article-title":"Metabolism of Entamoeba histolytica Schaudinn, 1903","volume":"23","author":"Reeves","year":"1984","journal-title":"Adv. Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1042\/bj1710225","article-title":"Pyruvate-to-ethanol pathway in Entamoeba histolytica","volume":"171","author":"Lo","year":"1978","journal-title":"Biochem. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1146\/annurev.mi.42.100188.002341","article-title":"Energy metabolism of protozoa without mitochondria","volume":"42","author":"Muller","year":"1988","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1042\/bj3030743","article-title":"Purification and molecular characterization of the NAD(+)-dependent acetaldehyde\/alcohol dehydrogenase from Entamoeba histolytica","volume":"303","author":"Bruchhaus","year":"1994","journal-title":"Biochem. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.molbiopara.2004.06.002","article-title":"Structural analysis of the acetaldehyde dehydrogenase activity of Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a member of the ADHE enzyme family","volume":"137","author":"Chen","year":"2004","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20136","DOI":"10.1074\/jbc.M101349200","article-title":"The bifunctional Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) protein is necessary for amebic growth and survival and requires an intact C-terminal domain for both alcohol dahydrogenase and acetaldehyde dehydrogenase activity","volume":"276","author":"Espinosa","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1099\/mic.0.040063-0","article-title":"Acetaldehyde\/alcohol dehydrogenase-2 (EhADH2) and clathrin are involved in internalization of human transferrin by Entamoeba histolytica","volume":"157","author":"Avila","year":"2011","journal-title":"Microbiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0020-711X(71)90041-3","article-title":"Nicotinamide-adenine dinucleotide phosphate-dependent alcohol dehydrogenase: The enzyme from Entamoeba histolytica and some inhibitors","volume":"2","author":"Reeves","year":"1971","journal-title":"Int. J. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2307\/3280944","article-title":"Purification and properties of NADP-linked, alcohol dehydrogenase from Entamoeba histolytica","volume":"68","author":"Lo","year":"1982","journal-title":"J. Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10188","DOI":"10.1073\/pnas.89.21.10188","article-title":"Cloning and expression of an NADP(+)-dependent alcohol dehydrogenase gene of Entamoeba histolytica","volume":"89","author":"Kumar","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","first-page":"31","article-title":"Primary structures of alcohol and aldehyde dehydrogenase genes of Entamoeba histolytica","volume":"23","author":"Samuelson","year":"1992","journal-title":"Arch. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0167-4781(96)00014-0","article-title":"Cloning and expression of an Entamoeba histolytica NAPD+(-)dependent alcohol dehydrogenase gene","volume":"1306","author":"Rodriguez","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1128\/cdli.3.3.270-274.1996","article-title":"Cloning and expression of a putative alcohol dehydrogenase gene of Entamoeba histolytica and its application to immunological examination","volume":"3","author":"Kimura","year":"1996","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Davis, P.H., Chen, M., Zhang, X., Clark, C.G., Townsend, R.R., and Stanley, S.L. (2009). Proteomic comparison of Entamoeba histolytica and Entamoeba dispar and the role of E. histolytica alcohol dehydrogenase 3 in virulence. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000415"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1046\/j.1365-2958.2000.02143.x","article-title":"Early lateral transfer of genes encoding malic enzyme, acetyl-CoA synthetase and alcohol dehydrogenases from anaerobic prokaryotes to Entamoeba histolytica","volume":"38","author":"Field","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1128\/EC.1.2.181-190.2002","article-title":"Evidence for lateral transfer of genes encoding ferredoxins, nitroreductases, NADH oxidase, and alcohol dehydrogenase 3 from anaerobic prokaryotes to Giardia lamblia and Entamoeba histolytica","volume":"1","author":"Nixon","year":"2002","journal-title":"Eukaryot. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/infdis\/173.1.226","article-title":"Surface localization, regulation, and biologic properties of the 96-kDa alcohol\/aldehyde dehydrogenase (EhADH2) of pathogenic Entamoeba histolytica","volume":"173","author":"Flores","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1074\/mcp.M113.031393","article-title":"The Cell Surface Proteome of Entamoeba histolytica","volume":"13","author":"Biller","year":"2014","journal-title":"Mol. Cell. Proteom."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Meyer, M., Fehling, H., Matthiesen, J., Lorenzen, S., Schuldt, K., Bernin, H., Zaruba, M., Lender, C., Ernst, T., and Ittrich, H. (2016). Overexpression of differentially expressed genes identified in non-pathogenic and pathogenic Entamoeba histolytica clones allow identification of new pathogenicity factors involved in amoebic liver abscess formation. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005853"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1096\/fj.201801313R","article-title":"Trigger-induced RNAi gene silencing to identify pathogenicity factors of Entamoeba histolytica","volume":"33","author":"Matthiesen","year":"2019","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0035-9203(78)90144-X","article-title":"A new medium for axenic cultivation of Entamoeba histolytica and other Entamoeba","volume":"72","author":"Diamond","year":"1978","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1002\/pmic.200900022","article-title":"Comparison of two genetically related Entamoeba histolytica cell lines derived from the same isolate with different pathogenic properties","volume":"9","author":"Biller","year":"2009","journal-title":"Proteomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1017\/S0031182000077040","article-title":"Spontaneous release of cysteine proteinases but not of pore-forming peptides by viable Entamoeba histolytica","volume":"111","author":"Leippe","year":"1995","journal-title":"Parasitology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0065-308X(07)65002-7","article-title":"Structure and content of the Entamoeba histolytica genome","volume":"65","author":"Clark","year":"2007","journal-title":"Adv. Parasitol."},{"key":"ref_26","first-page":"217","article-title":"Subcellular localization of the NAD+-dependent alcohol dehydrogenase in Entamoeba histolytica trophozoites","volume":"88","author":"Avila","year":"2002","journal-title":"J. Parasitol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0166-6851(93)00020-A","article-title":"Entamoeba histolytica has an alcohol dehydrogenase homologous to the multifunctional adhE gene product of Escherichia coli, Mol","volume":"64","author":"Yang","year":"1994","journal-title":"Biochem. Parasitol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8963","DOI":"10.1007\/s00253-013-4725-0","article-title":"Structural and biochemical characterisation of a NAD(+)-dependent alcohol dehydrogenase from Oenococcus oeni as a new model molecule for industrial biotechnology applications","volume":"97","author":"Elleuche","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00253-010-2912-9","article-title":"YqhD: A broad-substrate range aldehyde reductase with various applications in production of biorenewable fuels and chemicals","volume":"89","author":"Jarboe","year":"2011","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1007\/s00253-013-5374-z","article-title":"Group III alcohol dehydrogenase from Pectobacterium atrosepticum: Insights into enzymatic activity and organization of the metal ion-containing region","volume":"98","author":"Elleuche","year":"2014","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.jmb.2011.01.045","article-title":"Structures of iron-dependent alcohol dehydrogenase 2 from Zymomonas mobilis ZM4 with and without NAD+ cofactor","volume":"407","author":"Moon","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3109\/10408419409113545","article-title":"Molecular characterization of microbial alcohol dehydrogenases","volume":"20","author":"Reid","year":"1994","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.jmb.2004.07.034","article-title":"Crystal structure of E.coli alcohol dehydrogenase YqhD: Evidence of a covalently modified NADP coenzyme","volume":"342","author":"Sulzenbacher","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1006\/prep.1997.0742","article-title":"Purification of alcohol dehydrogenase from Entamoeba histolytica and Saccharomyces cerevisiae using zinc-affinity chromatography","volume":"10","author":"Cabrera","year":"1997","journal-title":"Protein Expr. Purif."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1093\/jac\/dkp015","article-title":"Effects of iron depletion on Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) and trophozoite growth: Implications for antiamoebic therapy","volume":"63","author":"Espinosa","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7346","DOI":"10.1074\/jbc.M708846200","article-title":"Escherichia coli YqhD exhibits aldehyde reductase activity and protects from the harmful effect of lipid peroxidation-derived aldehydes","volume":"283","author":"Perez","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1152\/physrev.00034.2014","article-title":"Metabolic methanol: Molecular pathways and physiological roles","volume":"95","author":"Dorokhov","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2302\/kjm.24.19","article-title":"Toxicity of formaldehyde in experimental animals--concentrations of the chemical in the elution from dishes of formaldehyde resin in some vegetables","volume":"24","author":"Tsuchiya","year":"1975","journal-title":"Keio J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1002\/jps.21319","article-title":"Your prodrug releases formaldehyde: Should you be concerned? No!","volume":"97","author":"Dhareshwar","year":"2008","journal-title":"J. Pharm. Sci."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/10\/1608\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:24:07Z","timestamp":1760178247000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/10\/1608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,19]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["microorganisms8101608"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms8101608","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,19]]}}}