{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:51:40Z","timestamp":1791316300112,"version":"4.3.1"},"reference-count":116,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Malaysian Ministry of Higher Education Fundamental research grant (FRGS)","award":["FRGS\/1\/2020\/STG01\/USM\/02\/11"],"award-info":[{"award-number":["FRGS\/1\/2020\/STG01\/USM\/02\/11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Entamoeba histolytica is a protozoan parasite that is the causative agent of amoebiasis. This parasite has caused widespread infection in India, Africa, Mexico, and Central and South America, and results in 100,000 deaths yearly. An immune response is a body's mechanism for eradicating and fighting against substances it sees as harmful or foreign. E. histolytica biological membranes are considered foreign and immunogenic to the human body, thereby initiating the body's immune responses. Understanding immune response and antigen interaction are essential for vaccine development. Thus, this review aims to identify and understand the protein structure, function, and interaction of the biological membrane with the immune response, which could contribute to vaccine development. Furthermore, the current trend of vaccine development studies to combat amoebiasis is also reviewed.<\/jats:p>","DOI":"10.3390\/membranes12111079","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T07:06:46Z","timestamp":1667200006000},"page":"1079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Entamoeba histolytica: Membrane and Non-Membrane Protein Structure, Function, Immune Response Interaction, and Vaccine Development"],"prefix":"10.3390","volume":"12","author":[{"given":"Nurhana","family":"Jasni","sequence":"first","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor 11800, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3868-0641","authenticated-orcid":false,"given":"Syazwan","family":"Saidin","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, Tanjung Malim 35900, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wong Weng","family":"Kin","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2729-8866","authenticated-orcid":false,"given":"Norsyahida","family":"Arifin","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor 11800, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1105-4509","authenticated-orcid":false,"given":"Nurulhasanah","family":"Othman","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Gelugor 11800, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"683157","DOI":"10.3389\/fimmu.2021.683157","article-title":"Optimizing a multi-component intranasal Entamoeba histolytica vaccine formulation using a design of experiments strategy","volume":"12","author":"Abhyankar","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_2","unstructured":"WHO\/PAHO\/UNESCO Report (1997). A consultation with experts on amoebiasis. Mexico City, Mexico 28\u201329 January, 1997. Epidemiol. Bull., 18, 13\u201314."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4601420","DOI":"10.1155\/2018\/4601420","article-title":"Entamoeba histolytica: Updates in clinical manifestation, pathogenesis, and vaccine development","volume":"2018","author":"Kantor","year":"2018","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.vaccine.2016.12.057","article-title":"Nanoformulation of synergistic TLR ligands to enhance vaccination against Entamoeba histolytica","volume":"35","author":"Abhyankar","year":"2017","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1128\/IAI.74.2.904-909.2006","article-title":"Entamoeba histolytica infection in children and protection from subsequent amebiasis","volume":"74","author":"Haque","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jinf.2009.05.008","article-title":"A global study of pathogens and host risk factors associated with infectious gastrointestinal disease in returned international travellers","volume":"59","author":"Swaminathan","year":"2009","journal-title":"J. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1128\/CMR.00004-07","article-title":"Laboratory diagnostic techniques for Entamoeba species","volume":"20","author":"Fotedar","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.4269\/ajtmh.20-0348","article-title":"Multi-laboratory evaluation of a lateral flow rapid test for detection of amebic liver abscess","volume":"103","author":"Noordin","year":"2020","journal-title":"Am. J. Trop. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10096-018-3379-3","article-title":"Update on laboratory diagnosis of amoebiasis","volume":"38","author":"Saidin","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1128\/IAI.67.5.2096-2102.1999","article-title":"Down regulation of Entamoeba histolytica virulence by monoxenic cultivation with Escherichia coli O55 is related to a decrease in expression of the light (35-kilodalton) subunit of the Gal\/GalNAc lectin","volume":"67","author":"Ankri","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_11","first-page":"301","article-title":"Current pharmacotherapy of amebiasis, advances in new drugs, and design of a vaccine","volume":"53","year":"2012","journal-title":"SCIELO"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"628257","DOI":"10.3389\/fcimb.2020.628257","article-title":"Revisiting drug development against the neglected tropical disease, amebiasis","volume":"10","author":"Shrivastav","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Moonah, S.N., Jiang, N.M., and Petri, W.A. (2013). Host immune response to intestinal amebiasis. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003489"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1152\/physiol.00038.2019","article-title":"Immune response to the enteric parasite Entamoeba histolytica","volume":"35","author":"Rosales","year":"2020","journal-title":"Physiol. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.3389\/fmicb.2015.01394","article-title":"Immune evasion mechanisms of Entamoeba histolytica: Progression to disease","volume":"6","author":"Begum","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_16","unstructured":"Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002). Innate Immunity. Molecular Biology of the Cell, Garland Science. [4th ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/0192623311431468","article-title":"Immunology for the toxicologic pathologist","volume":"40","author":"Snyder","year":"2012","journal-title":"Toxicol. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.4161\/hv.27796","article-title":"The future for vaccine development against Entamoeba histolytica","volume":"10","author":"Quach","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_19","first-page":"1","article-title":"Successful vaccines","volume":"428","author":"Amanna","year":"2020","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107679","DOI":"10.1016\/j.intimp.2021.107679","article-title":"Essential considerations during vaccine design against COVID-19 and review of pioneering vaccine candidate platforms","volume":"97","author":"Bayat","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Azmi, N., and Othman, N. (2021). Entamoeba histolytica: Proteomics bioinformatics reveal predictive functions and protein\u2013protein interactions of differentially abundant membrane and cytosolic proteins. Membranes, 11.","DOI":"10.3390\/membranes11060376"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.bbrc.2007.06.027","article-title":"MemType-2L: A web server for predicting membrane proteins and their types by incorporating evolution information through Pse-PSSM","volume":"360","author":"Chou","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Guo, L., Wang, S., Li, M., and Cao, Z. (2019). Accurate classification of membrane protein types based on sequence and evolutionary information using deep learning. BMC Bioinform., 20.","DOI":"10.1186\/s12859-019-3275-6"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53R","DOI":"10.1093\/glycob\/cwj007","article-title":"Roles for the galactose-\/N-acetylgalactosamine-binding lectin of Entamoeba in parasite virulence and differentiation","volume":"15","author":"Frederick","year":"2005","journal-title":"J. Glycobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0074-7696(02)16003-7","article-title":"Structure and function of the Entamoeba histolytica Gal\/GalNAc lectin","volume":"216","author":"Mann","year":"2002","journal-title":"Int. Rev. Cytol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1086\/314610","article-title":"Infection and immunity mediated by the carbohydrate recognition domain of the Entamoeba histolytica Gal\/GalNAc lectin","volume":"179","author":"Dodson","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5892","DOI":"10.1128\/IAI.69.9.5892-5898.2001","article-title":"Intermediate subunit of the Gal\/GalNAc lectin of Entamoeba histolytica is a member of a gene family containing multiple CXXC sequence motifs","volume":"69","author":"Cheng","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13901","DOI":"10.1038\/srep13901","article-title":"Novel hemagglutinating, hemolytic and cytotoxic activities of the intermediate subunit of Entamoeba histolytica lectin","volume":"5","author":"Kato","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Hern\u00e1ndez, J., Retana-Gonz\u00e1lez, C., Ramos-Mart\u00ednez, E., Cruz-Col\u00edn, J., Saralegui-Amaro, A., Baltazar-Rosario, G., Guti\u00e9rrez-Ru\u00edz, C., Aristi-Urista, G., and L\u00f3pez-Vancell, R. (2021). Entamoeba histolytica trophozoites interact with the c-Met receptor at the surface of liver origin cells through the Gal\/GalNAc amoebic lectin. Life, 11.","DOI":"10.3390\/life11090923"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Welter, B.H., Walters, H.A., and Temesvari, L.A. (2020). Reduced expression of a rhomboid protease, EhROM1, correlates with changes in the submembrane distribution and size of the Gal\/GalNAc lectin subunits in the human protozoan parasite, Entamoeba histolytica. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0219870"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kato, K., and Tachibana, H. (2022). Identification of multiple domains of Entamoeba histolytica intermediate subunit lectin-1 with hemolytic and cytotoxic activities. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147700"},{"key":"ref_32","first-page":"175","article-title":"Immune response of amebiasis and immune evasion by Entamoeba histolytica","volume":"7","author":"Nozaki","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41541-018-0060-x","article-title":"Adjuvant composition and delivery route shape immune response quality and protective efficacy of a recombinant vaccine for Entamoeba histolytica","volume":"3","author":"Abhyankar","year":"2018","journal-title":"NPJ Vaccines"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s10529-017-2341-2","article-title":"An anti-amoebic vaccine: Generation of the recombinant antigen LC3 from Entamoeba histolytica linked to mutated exotoxin A (PE\u0394III) via the Pichia pastoris system","volume":"39","year":"2017","journal-title":"Biotechnol. Lett."},{"key":"ref_35","first-page":"6697900","article-title":"Evaluation of the PE\u0394III-LC3-KDEL3 chimeric protein of Entamoeba histolytica-lectin as a vaccine candidate against amebic liver abscess","volume":"2021","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.7150\/ijbs.7.1345","article-title":"Mucosal delivery of ACNPV baculovirus driving expression of the Gal-lectin LC3 fragment confers protection against amoebic liver abscess in hamster","volume":"7","author":"Laclette","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"ref_37","first-page":"760598","article-title":"Protection against amoebic liver abscess in hamster by intramuscular immunization with an Autographa californica baculovirus driving the expression of the Gal-lectin LC3 fragment","volume":"2015","author":"Bobes","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kato, K., Makiuchi, T., Cheng, X., and Tachibana, H. (2017). Comparison of hemolytic activity of the intermediate subunit of Entamoeba histolytica and Entamoeba dispar lectins. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181864"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Min, X., Feng, M., Guan, Y., Man, S., Fu, Y., Cheng, X., and Tachibana, H. (2016). Evaluation of the c-terminal fragment of Entamoeba histolytica Gal\/GalNAc lectin intermediate subunit as a vaccine candidate against amebic liver abscess. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004419"},{"key":"ref_40","unstructured":"UNIPROT (2022, September 19). Gal\/GalNAc Lectin Igl1. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q964D2\/entry."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1128\/EC.2.3.501-509.2003","article-title":"The intestinal protozoan parasite Entamoeba histolytica contains 20 cysteine protease genes, of which only a small subset is expressed during in vitro cultivation","volume":"2","author":"Bruchhaus","year":"2003","journal-title":"Eukaryot. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"18516","DOI":"10.1074\/jbc.M109.086181","article-title":"A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target","volume":"285","author":"He","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1128\/EC.00094-07","article-title":"Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model","volume":"6","author":"Herdman","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1017\/S0031182004005451","article-title":"Role of cysteine proteinase of Entamoeba histolytica in target cell death","volume":"129","author":"Singh","year":"2004","journal-title":"J. Parasitol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1017\/S003118201500147X","article-title":"The knockdown of each component of the cysteine proteinase-adhesin complex of Entamoeba histolytica (EhCPADH) affects the expression of the other complex element as well as the in vitro and in vivo virulence","volume":"143","author":"Fonseca","year":"2016","journal-title":"J. Parasitol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.pep.2008.09.006","article-title":"Purification, refolding and autoactivation of the recombinant cysteine proteinase EhCP112 from Entamoeba histolytica","volume":"63","author":"Orozco","year":"2009","journal-title":"Protein Expr. Purif."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cornick, S., Moreau, F., and Chadee, K. (2016). Entamoeba histolytica cysteine proteinase 5 evokes mucin exocytosis from colonic goblet cells via \u03b1v\u03b23 integrin. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005579"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"35497","DOI":"10.1074\/jbc.M109.066035","article-title":"Entamoeba histolytica cysteine proteinase 5 binds integrin on colonic cells and stimulates NFkappaB-mediated pro-inflammatory responses","volume":"285","author":"Hou","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_50","unstructured":"UNIPROT (2022, September 19). Cysteine Proteinase 5. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q06FF8\/entry."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lotter, H., Gonz\u00e1lez-Rold\u00e1n, N., Lindner, B., Winau, F., Isibasi, A., Moreno-Lafont, M., Ulmer, A.J., Holst, O., Tannich, E., and Jacobs, T. (2009). Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000434"},{"key":"ref_52","first-page":"254521","article-title":"The role of lipopeptidophosphoglycan in the immune response to Entamoeba histolytica","volume":"2010","author":"Isibasi","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1017\/S0031182096008396","article-title":"Virulent and avirulent Entamoeba histolytica and Entamoeba dispar differ in their cell surface phosphorylated glycolipids","volume":"114","author":"Moody","year":"1997","journal-title":"J. Parasitol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1365-3024.2005.00754.x","article-title":"The innate immune response to Entamoeba histolytica lipopeptidophosphoglycan is mediated by toll-like receptors 2 and 4","volume":"27","author":"Kirschning","year":"2005","journal-title":"Parasite Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1365-3024.2007.00963.x","article-title":"Lipopopeptidephosphoglycan from Entamoeba histolytica activates human macrophages and dendritic cells and reaches their late endosomes","volume":"29","author":"Isibasi","year":"2007","journal-title":"Parasite Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"\u00c1vila, E.E., Salaiza, N., Pulido, J., Rodr\u00edguez, M.C., D\u00edaz-God\u00ednez, C., Laclette, J.P., Becker, I., and Carrero, J.C. (2016). Entamoeba histolytica trophozoites and lipopeptidophosphoglycan trigger human neutrophil extracellular traps. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158979"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/20477724.2020.1780402","article-title":"Antigenic membrane proteins of virulent variant of Entamoeba histolytica HM-1:IMSS","volume":"114","author":"Kumarasamy","year":"2020","journal-title":"Pathog. Glob. Health"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"286972","DOI":"10.1155\/2015\/286972","article-title":"Analysis of the isomerase and chaperone-like activities of an amebic PDI (EhPDI)","volume":"2015","author":"Mares","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.parint.2009.04.001","article-title":"Oxidative folding and reductive activities of EhPDI, a protein disulfide isomerase from Entamoeba histolytica","volume":"58","author":"Mares","year":"2009","journal-title":"Parasitol. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.exppara.2011.02.009","article-title":"Entamoeba histolytica: Biochemical characterization of a protein disulfide isomerase","volume":"128","author":"Ramos","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/2211-5463.12350","article-title":"An amebic protein disulfide isomerase (PDI) complements the yeast PDI1 mutation but is unable to support cell viability under ER or thermal stress","volume":"8","author":"Mares","year":"2018","journal-title":"FEBS Open Bio"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.molimm.2016.12.022","article-title":"Immunization with Leishmania donovani protein disulfide isomerase DNA construct induces Th1 and Th17 dependent immune response and protection against experimental Visceral leishmaniasis in BALB\/c mice","volume":"82","author":"Amit","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_63","unstructured":"UNIPROT (2022, September 19). Protein Disulfide Isomerase. Available online: https:\/\/www.uniprot.org\/uniprotkb\/A0A5K1UZD0\/entry."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/1756-3305-5-224","article-title":"A Toll\/IL-1R\/resistance domain-containing thioredoxin regulates phagocytosis in Entamoeba histolytica","volume":"5","year":"2012","journal-title":"Parasites Vectors"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ijpddr.2017.09.001","article-title":"Drug susceptibility testing in microaerophilic parasites: Cysteine strongly affects the effectivities of metronidazole and auranofin, a novel and promising antimicrobial","volume":"7","author":"Leitsch","year":"2017","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"975","DOI":"10.3389\/fmicb.2015.00975","article-title":"New drug target in protozoan parasites: The role of thioredoxin reductase","volume":"6","author":"Andrade","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1042\/BST0331375","article-title":"Thiol redox control via thioredoxin and glutaredoxin systems","volume":"33","author":"Holmgren","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_68","unstructured":"UNIPROT (2022, September 19). Thioredoxin, Putative. Available online: https:\/\/www.uniprot.org\/uniprotkb\/S0AYD1\/entry."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e12812","DOI":"10.1111\/pim.12812","article-title":"Glycan moieties in Entamoeba histolytica ubiquitin are immunodominant","volume":"43","author":"Flores","year":"2021","journal-title":"Parasite Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0014-5793(92)81049-R","article-title":"Ubiquitin of Entamoeba histolytica deviates in six amino acid residues from the consensus of all other known ubiquitins","volume":"308","author":"Tannich","year":"1992","journal-title":"FEBS Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.exppara.2018.11.003","article-title":"Characterization of N-glycosylations in Entamoeba histolytica ubiquitin","volume":"196","author":"Flores","year":"2019","journal-title":"Exp. Parasitol."},{"key":"ref_72","first-page":"2290","article-title":"Structural determinants of ubiquitin conjugation in Entamoeba histolytica","volume":"288","author":"Bosch","year":"2013","journal-title":"Exp. Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e12919","DOI":"10.1111\/pim.12919","article-title":"Ubiquitin of Entamoeba histolytica induces antibody response in patients with invasive amoebiasis","volume":"44","author":"Flores","year":"2022","journal-title":"Parasite Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00436-010-2085-6","article-title":"Entamoeba histolytica calreticulin: An endoplasmic reticulum protein expressed by trophozoites into experimentally induced amoebic liver abscesses","volume":"108","author":"Meza","year":"2011","journal-title":"Parasitol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"358","DOI":"10.3389\/fcimb.2018.00358","article-title":"Entamoeba histolytica calreticulin induces the expression of cytokines in peripheral blood mononuclear cells isolated from patients with amebic liver abscess","volume":"8","author":"Ximenez","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.molbiopara.2007.10.014","article-title":"The endoplasmic reticulum chaperone calreticulin is recruited to the uropod during capping of surface receptors in Entamoeba histolytica","volume":"157","author":"Sachse","year":"2008","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_77","first-page":"127453","article-title":"Entamoeba histolytica and E. dispar calreticulin: Inhibition of classical complement pathway and differences in the level of expression in amoebic liver abscess","volume":"2014","author":"Nieves","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_78","unstructured":"UNIPROT (2022, September 19). Calreticulin. Available online: https:\/\/www.uniprot.org\/uniprotkb\/C4M296\/entry."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1128\/IAI.01812-14","article-title":"The macrophage migration inhibitory factor homolog of Entamoeba histolytica binds to and immunomodulates host macrophages","volume":"82","author":"Moonah","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1093\/infdis\/jix076","article-title":"Entamoeba histolytica-encoded homolog of macrophage migration inhibitory factor contributes to mucosal inflammation during amoebic colitis","volume":"215","author":"Ngobeni","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/infdis\/jiz579","article-title":"Targeting parasite-produced macrophage migration inhibitory factor as an antivirulence strategy with antibiotic-antibody combination to reduce tissue damage","volume":"221","author":"Ghosh","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10241","DOI":"10.1038\/s41598-018-28625-1","article-title":"Interaction between parasite-encoded JAB1\/CSN5 and macrophage migration inhibitory factor proteins attenuates its proinflammatory function","volume":"8","author":"Ghosh","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_83","unstructured":"UNIPROT (2022, September 19). Migration Inhibitory Factor Protein. Available online: https:\/\/www.uniprot.org\/uniprotkb\/A0A5K1URL6\/entry."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e00349-20","DOI":"10.1128\/IAI.00349-20","article-title":"Characterization of extracellular vesicles from Entamoeba histolytica identifies roles in intercellular communication that regulates parasite growth and development","volume":"88","author":"Sharma","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.molimm.2021.02.007","article-title":"Unveiling the role of EVs in anaerobic parasitic protozoa","volume":"133","author":"Sabatke","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e13257","DOI":"10.1111\/cmi.13257","article-title":"Extracellular vesicles released by anaerobic protozoan parasites: Current situation","volume":"22","author":"Nievas","year":"2020","journal-title":"Cell. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Tovy, A., Siman Tov, R., Gaentzsch, R., Helm, M., and Ankri, S. (2010). A new nuclear function of the Entamoeba histolytica glycolytic enzyme enolase: The metabolic regulation of cytosine-5 methyltransferase 2 (Dnmt2) activity. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000775"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1574-6968.1997.tb10277.x","article-title":"Molecular characterization of the Entamoeba histolytica enolase gene and modelling of the predicted protein","volume":"148","author":"Hidalgo","year":"1997","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1107\/S0907444911016544","article-title":"Structure analysis of Entamoeba histolytica enolase","volume":"67","author":"Schulz","year":"2011","journal-title":"Acta Crystallogr. D"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Xue, S., Seo, K., Yang, M., Cui, C., Yang, M., Xiang, S., Yan, Z., Wu, S., Han, J., and Yu, X. (2021). Mycoplasma suis alpha-enolase subunit vaccine induces an immune response in experimental animals. Vaccines, 9.","DOI":"10.3390\/vaccines9121506"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"T\u00e9llez-Mart\u00ednez, D., Leandro Portuondo, D., Loesch, M.L., Batista-Duharte, A., and Zeppone Carlos, I. (2019). A recombinant enolase-montanide\u2122 petgel a vaccine promotes a protective Th1 immune response against a highly virulent Sporothrix schenckii by toluene exposure. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11030144"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.fsi.2016.10.011","article-title":"Immune response induced by oral delivery of Bacillus subtilis spores expressing enolase of Clonorchis sinensis in grass carps (Ctenopharyngodon idellus)","volume":"60","author":"Jiang","year":"2017","journal-title":"Fish Shellfish Immunol."},{"key":"ref_93","unstructured":"DataBank, P. (2022, October 25). Enolase 1. Available online: https:\/\/www.ebi.ac.uk\/pdbe\/entry\/pdb\/3qtp\/analysis."},{"key":"ref_94","unstructured":"DataBank, P. (2022, October 25). Pfam Enolase, N-Terminal Domain. Available online: https:\/\/www.ebi.ac.uk\/pdbe\/entry\/view3D\/3qtp\/?view=entry_index&viewer=litemol."},{"key":"ref_95","unstructured":"DataBank, P. (2022, October 25). Pfam Enolase, C-Terminal Tim Barrel Domain. Available online: https:\/\/www.ebi.ac.uk\/pdbe\/entry\/view3D\/3qtp\/?view=entry_index&viewer=litemol."},{"key":"ref_96","first-page":"e12983","article-title":"Acetylation is the most abundant actin modification in Entamoeba histolytica and modifications of actin\u2019s amino-terminal domain change cytoskeleton activities","volume":"21","author":"Jhingan","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref_97","first-page":"360","article-title":"A bioinformatics approach to designing a multi-variant vaccine against Entamoeba histolytica","volume":"5","author":"Adeoti","year":"2021","journal-title":"Biomed. Res. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/prot.25955","article-title":"The actin cytoskeleton orchestra in Entamoeba histolytica","volume":"88","author":"Rath","year":"2020","journal-title":"Proteins Struct. Funct. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1021\/acs.jnatprod.0c00892","article-title":"Linearolactone and kaempferol disrupt the actin cytoskeleton in Entamoeba histolytica: Inhibition of amoebic liver abscess development","volume":"83","author":"Calzada","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_100","first-page":"169","article-title":"Antiamoebic activity of Adenophyllum aurantium (L.) Strother and its effect on the actin cytoskeleton of Entamoeba histolytica","volume":"7","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetpar.2011.03.003","article-title":"Immune response and protective efficacy against homologous challenge in BALB\/c mice vaccinated with DNA vaccine encoding Toxoplasma gondii actin depolymerizing factor gene","volume":"179","author":"Li","year":"2011","journal-title":"Vet. Parasitol."},{"key":"ref_102","unstructured":"UNIPROT (2022, September 19). Actin. Available online: https:\/\/www.uniprot.org\/uniprotkb\/P11426\/entry."},{"key":"ref_103","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_104","doi-asserted-by":"crossref","unstructured":"K\u00f6nig, C., Meyer, M., Lender, C., Nehls, S., Wallaschkowski, T., Holm, T., Matthies, T., Lercher, D., Matthiesen, J., and Fehling, H. (2020). An alcohol dehydrogenase 3 (ADH3) from Entamoeba histolytica is involved in the detoxification of toxic aldehydes. Microorganisms, 8.","DOI":"10.3390\/microorganisms8101608"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"603.23","DOI":"10.1096\/fasebj.31.1_supplement.603.23","article-title":"Prediction of the Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) protein structure using bioinformatics tools","volume":"31","author":"Lowerre","year":"2017","journal-title":"FASEB J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"606.16","DOI":"10.1096\/fasebj.31.1_supplement.606.16","article-title":"Structural and biochemical analyses of alcohol dehydrogenase E enzymes from Entamoeba invadens IP-1, E. invadens VK-1:NS and E. dispar","volume":"31","author":"Gabrielle","year":"2017","journal-title":"FASEB J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"921.4","DOI":"10.1096\/fasebj.31.1_supplement.921.4","article-title":"Inhibitory effects of substituted pyrazoline derivatives on Entamoeba histolytica alcohol and acetaldehyde dehydrogenase (EhADH2) activities","volume":"31","author":"Hackey","year":"2017","journal-title":"FASEB J."},{"key":"ref_108","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_109","doi-asserted-by":"crossref","first-page":"722.1","DOI":"10.1096\/fasebj.29.1_supplement.722.1","article-title":"Isolation and purification of Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) enzymatic activities and inhibition by pyrazoline derivatives","volume":"29","author":"Leitao","year":"2015","journal-title":"FASEB J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/jac\/dkh280","article-title":"Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) as a target for anti-amoebic agents","volume":"54","author":"Espinosa","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s00436-002-0716-2","article-title":"Nitric oxide inhibits cysteine proteinases and alcohol dehydrogenase 2 of Entamoeba histolytica","volume":"89","author":"Ankri","year":"2003","journal-title":"Parasitol. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1365-2583.2004.00543.x","article-title":"A role for alcohol dehydrogenase in the Drosophila immune response?","volume":"14","author":"Schlenke","year":"2005","journal-title":"Insect Mol. Biol."},{"key":"ref_113","unstructured":"UNIPROT (2022, September 19). Alcohol Dehydrogenase 3. Available online: https:\/\/www.uniprot.org\/uniprotkb\/Q24857\/entry."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.4155\/fmc-2016-0143","article-title":"Molecular docking for drug discovery and development: A widely used approach but far from perfect","volume":"8","author":"Wang","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular docking: A powerful approach for structure-based drug discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Kumar, S. (2020). Drug and vaccine design against novel coronavirus (2019-nCoV) spike protein through computational approach. Preprints.","DOI":"10.20944\/preprints202002.0071.v1"}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/12\/11\/1079\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:06:37Z","timestamp":1760144797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/12\/11\/1079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":116,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["membranes12111079"],"URL":"https:\/\/doi.org\/10.3390\/membranes12111079","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,31]]}}}