{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:55:41Z","timestamp":1781189741225,"version":"3.54.1"},"reference-count":27,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,2]],"date-time":"2018-12-02T00:00:00Z","timestamp":1543708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2011\/12928-2"],"award-info":[{"award-number":["2011\/12928-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/17006-2"],"award-info":[{"award-number":["2017\/17006-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["PNPD20132071"],"award-info":[{"award-number":["PNPD20132071"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Agency for Promotion of Science and Technology","award":["ANPCYT-PICT 2016-0292"],"award-info":[{"award-number":["ANPCYT-PICT 2016-0292"]}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["CONICET, PIP354"],"award-info":[{"award-number":["CONICET, PIP354"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"University of Buenos Aires","doi-asserted-by":"publisher","award":["UBACYT-770"],"award-info":[{"award-number":["UBACYT-770"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"University of Buenos Aires","doi-asserted-by":"publisher","award":["PDE 5-2017"],"award-info":[{"award-number":["PDE 5-2017"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible for causing hemolytic uremic syndrome (HUS), a life-threatening thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and acute renal failure after bacterially induced hemorrhagic diarrhea. Until now, there has been neither an effective treatment nor method of prevention for the deleterious effects caused by Stx intoxication. Antibodies are well recognized as affinity components of therapeutic drugs; thus, a previously obtained recombinant human FabC11:Stx2 fragment was used to neutralize Stx2 in vitro in a Vero cell viability assay. Herein, we demonstrated that this fragment neutralized, in a dose-dependent manner, the cytotoxic effects of Stx2 on human glomerular endothelial cells, on human proximal tubular epithelial cells, and prevented the morphological alterations induced by Stx2. FabC11:Stx2 protected mice from a lethal dose of Stx2 by toxin-antibody pre-incubation. Altogether, our results show the ability of a new encouraging molecule to prevent Stx-intoxication symptoms during STEC infection.<\/jats:p>","DOI":"10.3390\/toxins10120508","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T06:02:09Z","timestamp":1543816929000},"page":"508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Human Recombinant Fab Fragment Neutralizes Shiga Toxin Type 2 Cytotoxic Effects in vitro and in vivo"],"prefix":"10.3390","volume":"10","author":[{"given":"Daniela","family":"Luz","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Bacteriologia, Instituto Butantan, S\u00e3o Paulo 05503900, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Marta","family":"Amaral","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiopatogenia, Departamento de Fisiolog\u00eda, Instituto de Fisiolog\u00eda y Biof\u00edsica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Sacerdoti","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiopatogenia, Departamento de Fisiolog\u00eda, Instituto de Fisiolog\u00eda y Biof\u00edsica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Mauro","family":"Bernal","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX)-CONICET-Academia Nacional de Medicina, Buenos Aires C1425, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-8184","authenticated-orcid":false,"given":"Wagner","family":"Quintilio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biof\u00e1rmacos em C\u00e9lulas Animais, Instituto Butantan, S\u00e3o Paulo, SP 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0650-7764","authenticated-orcid":false,"given":"Ana Maria","family":"Moro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biof\u00e1rmacos em C\u00e9lulas Animais, Instituto Butantan, S\u00e3o Paulo, SP 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Sandra","family":"Palermo","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX)-CONICET-Academia Nacional de Medicina, Buenos Aires C1425, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-501X","authenticated-orcid":false,"given":"Cristina","family":"Ibarra","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiopatogenia, Departamento de Fisiolog\u00eda, Instituto de Fisiolog\u00eda y Biof\u00edsica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-8506","authenticated-orcid":false,"given":"Roxane Maria Fontes","family":"Piazza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bacteriologia, Instituto Butantan, S\u00e3o Paulo 05503900, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s40203-017-0022-4","article-title":"In silico analysis of Shiga toxins (Stxs) to identify new potential vaccine targets for Shiga toxin-producing Escherichia coli","volume":"5","author":"Golshani","year":"2017","journal-title":"In Silico Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1099\/mic.0.000003","article-title":"Shiga toxins and stx phages: Highly diverse entities","volume":"161","author":"Lucchesi","year":"2015","journal-title":"Microbiology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kavaliauskiene, S., Lingelem, A.B.D., Skotland, T., and Sandvig, K. (2017). Protection against Shiga Toxins. Toxins, 9.","DOI":"10.3390\/toxins9020044"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hall, G., Kurosawa, S., and Stearns-Kurosawa, D.J. (2017). Shiga Toxin Therapeutics: Beyond Neutralization. Toxins, 9.","DOI":"10.3390\/toxins9090291"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/joim.12546","article-title":"Haemolytic uraemic syndrome","volume":"281","author":"Karpman","year":"2017","journal-title":"J. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1007\/s00467-012-2383-6","article-title":"Long-term outcomes of Shiga toxin hemolytic uremic syndrome","volume":"28","author":"Spinale","year":"2013","journal-title":"Pediatr. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.toxicon.2015.08.021","article-title":"Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells","volume":"105","author":"Girard","year":"2015","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Keenswijk, W. (2018). Eculizumab is Efficacious but Often Not Accessible. J. Pediatr. Hematol. Oncol.","DOI":"10.1097\/00043426-900000000-97855"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"24913","DOI":"10.1038\/srep24913","article-title":"Development of camelid single chain antibodies against Shiga toxin type 2 (Stx2) with therapeutic potential against Hemolytic Uremic Syndrome (HUS)","volume":"6","author":"Hiriart","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_10","first-page":"5","article-title":"New therapeutic developments against Shiga toxin-producing Escherichia coli","volume":"2","year":"2014","journal-title":"Microbiol. Spectrum"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.3390\/toxins2122769","article-title":"Escherichia coli Shiga Toxin Mechanisms of Action in Renal Disease","volume":"2","author":"Obrig","year":"2010","journal-title":"Toxins"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-1-4939-7447-4_3","article-title":"Construction of Synthetic Antibody Phage-Display Libraries","volume":"Volume 1701","author":"Hust","year":"2018","journal-title":"Phage Display: Methods and Protocols, Methods in Molecular Biology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Luz, D., Chen, G., Maranh\u00e3o, A.Q., Rocha, L.B., Sidhu, S., and Piazza, R.M.F. (2015). Development and Characterization of Recombinant Antibody Fragments That Recognize and Neutralize In Vitro Stx2 Toxin from Shiga Toxin-Producing Escherichia coli. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120481"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.jmb.2005.03.041","article-title":"Molecular Recognition by a Binary Code","volume":"348","author":"Fellouse","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3390\/toxins4090729","article-title":"Interaction between Shiga Toxin and Monoclonal Antibodies: Binding Characteristics and in Vitro Neutralizing Abilities","volume":"4","author":"Rocha","year":"2012","journal-title":"Toxins"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Amaral, M.M., Sacerdoti, F., Jancic, C., Repetto, H.A., Paton, A.W., Paton, J.C., and Ibarra, C. (2013). Action of Shiga Toxin Type-2 and Subtilase Cytotoxin on Human Microvascular Endothelial Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070431"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1348-0421.1999.tb02413.x","article-title":"In Vitro Assessment of a Chemically Synthesized Shiga Toxin Receptor Analog Attached to Chromosorb P (Synsorb Pk) as a Specific Absorbing Agent of Shiga Toxin 1 and 2","volume":"43","author":"Takeda","year":"1999","journal-title":"Microbiol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1128\/AAC.00343-09","article-title":"Safety and Pharmacokinetics of Urtoxazumab, a Humanized Monoclonal Antibody, against Shiga-Like Toxin 2 in Healthy Adults and in Pediatric Patients Infected with Shiga-Like Toxin-Producing Escherichia coli","volume":"54","author":"Lopez","year":"2010","journal-title":"Antimicrob. Ag. Chemot."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1128\/AAC.01661-08","article-title":"Safety and Pharmacokinetics of Chimeric Anti-Shiga Toxin 1 and Anti-Shiga Toxin 2 Monoclonal Antibodies in Healthy Volunteers","volume":"53","author":"Bitzan","year":"2009","journal-title":"Antimicrob. Ag. Chemot."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-1-62703-992-5_8","article-title":"Design and Generation of Synthetic Antibody Libraries for Phage Display","volume":"Volume 1131","author":"Ossipow","year":"2014","journal-title":"Monoclonal Antibodies: Methods and Protocols, Methods in Molecular Biology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nchembio843","article-title":"Synthetic therapeutic antibodies","volume":"2","author":"Sidhu","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.bbapap.2014.08.016","article-title":"Antibodies and protein misfolding: From structural research tools to therapeutic strategie","volume":"1844","author":"Genst","year":"2014","journal-title":"Biochim. Biophs. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1046\/j.1471-4159.1999.02002.x","article-title":"Transport of Cationized Anti-Tetanus Fab92 Fragments Across an In Vitro Blood\u2013Brain Barrier Model: Involvement of the Transcytosis Pathway","volume":"73","author":"Girod","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1128\/IAI.00867-09","article-title":"Toxin 2 Human Monoclonal Antibody against Shiga and Isotype Variants of a Recombinant Evaluation of Fab and F(ab)2","volume":"78","author":"Akiyoshi","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12369","DOI":"10.1073\/pnas.0913667107","article-title":"Paradoxical glomerular filtration of carbon nanotubes","volume":"107","author":"Ruggiero","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fernandez-Brando, R.J., Bentancor, L.V., Mej\u00edas, M.P., Ramos, M.V., Exeni, A., Exeni, C., Laso Mdel, C., Exeni, R., Isturiz, M.A., and Palermo, M.S. (2011). Antibody Response to Shiga Toxins in Argentinean Children with Enteropathic Hemolytic Uremic Syndrome at Acute and Long-Term Follow-Up Periods. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019136"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.micinf.2005.07.005","article-title":"Cytotoxic effect of Shiga toxin-2 holotoxin and its B subunit on human renal tubular epithelial cells","volume":"8","author":"Creydt","year":"2006","journal-title":"Microbes Infect."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/12\/508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:33:56Z","timestamp":1760196836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/12\/508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,2]]},"references-count":27,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["toxins10120508"],"URL":"https:\/\/doi.org\/10.3390\/toxins10120508","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,2]]}}}