Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo

Autores
Luz, Daniela; Amaral, María Marta; Sacerdoti, Flavia; Bernal, Alan Mauro; Quintilio, Wagner; Moro, Ana Maria; Palermo, Marina Sandra; Ibarra, Cristina Adriana; Piazza, Roxane Maria Fontes
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Luz, Daniela. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Bernal, Alan Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Quintilio, Wagner. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Moro, Ana Maria. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Piazza, Roxane Maria Fontes. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Materia
FAB
NEUTRALIZATION
PROTECTION
RECOMBINANT ANTIBODY FRAGMENT
SHIGA TOXIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/87969
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/87969
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivoLuz, DanielaAmaral, María MartaSacerdoti, FlaviaBernal, Alan MauroQuintilio, WagnerMoro, Ana MariaPalermo, Marina SandraIbarra, Cristina AdrianaPiazza, Roxane Maria FontesFABNEUTRALIZATIONPROTECTIONRECOMBINANT ANTIBODY FRAGMENTSHIGA TOXINhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Shiga 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.Fil: Luz, Daniela. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Bernal, Alan Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Quintilio, Wagner. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Moro, Ana Maria. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Piazza, Roxane Maria Fontes. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilMDPI2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87969Luz, Daniela; Amaral, María Marta; Sacerdoti, Flavia; Bernal, Alan Mauro; Quintilio, Wagner; et al.; Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo; MDPI; Toxins; 10; 12; 12-2018; 1-102072-6651CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/toxins10120508info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6651/10/12/508info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:41Zoai:ri.conicet.gov.ar:11336/87969instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:41.834CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
title Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
spellingShingle Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
Luz, Daniela
FAB
NEUTRALIZATION
PROTECTION
RECOMBINANT ANTIBODY FRAGMENT
SHIGA TOXIN
title_short Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
title_full Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
title_fullStr Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
title_full_unstemmed Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
title_sort Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo
dc.creator.none.fl_str_mv Luz, Daniela
Amaral, María Marta
Sacerdoti, Flavia
Bernal, Alan Mauro
Quintilio, Wagner
Moro, Ana Maria
Palermo, Marina Sandra
Ibarra, Cristina Adriana
Piazza, Roxane Maria Fontes
author Luz, Daniela
author_facet Luz, Daniela
Amaral, María Marta
Sacerdoti, Flavia
Bernal, Alan Mauro
Quintilio, Wagner
Moro, Ana Maria
Palermo, Marina Sandra
Ibarra, Cristina Adriana
Piazza, Roxane Maria Fontes
author_role author
author2 Amaral, María Marta
Sacerdoti, Flavia
Bernal, Alan Mauro
Quintilio, Wagner
Moro, Ana Maria
Palermo, Marina Sandra
Ibarra, Cristina Adriana
Piazza, Roxane Maria Fontes
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FAB
NEUTRALIZATION
PROTECTION
RECOMBINANT ANTIBODY FRAGMENT
SHIGA TOXIN
topic FAB
NEUTRALIZATION
PROTECTION
RECOMBINANT ANTIBODY FRAGMENT
SHIGA TOXIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Luz, Daniela. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Bernal, Alan Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Quintilio, Wagner. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Moro, Ana Maria. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Piazza, Roxane Maria Fontes. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasil
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/87969
Luz, Daniela; Amaral, María Marta; Sacerdoti, Flavia; Bernal, Alan Mauro; Quintilio, Wagner; et al.; Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo; MDPI; Toxins; 10; 12; 12-2018; 1-10
2072-6651
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87969
identifier_str_mv Luz, Daniela; Amaral, María Marta; Sacerdoti, Flavia; Bernal, Alan Mauro; Quintilio, Wagner; et al.; Human recombinant fab fragment neutralizes shiga toxin type 2 cytotoxic effects in vitro and in vivo; MDPI; Toxins; 10; 12; 12-2018; 1-10
2072-6651
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/toxins10120508
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6651/10/12/508
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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