Next Article in Journal
Human Monoclonal scFvs that Neutralize Fribrinogenolytic Activity of Kaouthiagin, a Zinc-Metalloproteinase in Cobra (Naja kaouthia) Venom
Previous Article in Journal
The Modes of Action of MARTX Toxin Effector Domains
Previous Article in Special Issue
Shiga Toxin Glycosphingolipid Receptors in Human Caco-2 and HCT-8 Colon Epithelial Cell Lines
 
 
Article

Human Recombinant Fab Fragment Neutralizes Shiga Toxin Type 2 Cytotoxic Effects in vitro and in vivo

1
Laboratório de Bacteriologia, Instituto Butantan, São Paulo 05503900, Brasil
2
Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121, Argentina
3
Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX)-CONICET-Academia Nacional de Medicina, Buenos Aires C1425, Argentina
4
Laboratório de Biofármacos em Células Animais, Instituto Butantan, São Paulo, SP 05503-900, Brazil
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Toxins 2018, 10(12), 508; https://doi.org/10.3390/toxins10120508
Received: 25 September 2018 / Revised: 24 November 2018 / Accepted: 28 November 2018 / Published: 2 December 2018
(This article belongs to the Collection Shiga Toxins)
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. View Full-Text
Keywords: Shiga toxin; recombinant antibody fragment; Fab; neutralization; protection Shiga toxin; recombinant antibody fragment; Fab; neutralization; protection
Show Figures

Figure 1

MDPI and ACS Style

Luz, D.; Amaral, M.M.; Sacerdoti, F.; Bernal, A.M.; Quintilio, W.; Moro, A.M.; Palermo, M.S.; Ibarra, C.; Piazza, R.M.F. Human Recombinant Fab Fragment Neutralizes Shiga Toxin Type 2 Cytotoxic Effects in vitro and in vivo. Toxins 2018, 10, 508. https://doi.org/10.3390/toxins10120508

AMA Style

Luz D, Amaral MM, Sacerdoti F, Bernal AM, Quintilio W, Moro AM, Palermo MS, Ibarra C, Piazza RMF. Human Recombinant Fab Fragment Neutralizes Shiga Toxin Type 2 Cytotoxic Effects in vitro and in vivo. Toxins. 2018; 10(12):508. https://doi.org/10.3390/toxins10120508

Chicago/Turabian Style

Luz, Daniela, Maria Marta Amaral, Flavia Sacerdoti, Alan Mauro Bernal, Wagner Quintilio, Ana Maria Moro, Marina Sandra Palermo, Cristina Ibarra, and Roxane Maria Fontes Piazza. 2018. "Human Recombinant Fab Fragment Neutralizes Shiga Toxin Type 2 Cytotoxic Effects in vitro and in vivo" Toxins 10, no. 12: 508. https://doi.org/10.3390/toxins10120508

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop