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

Author(s)

Luz, Daniela ^[1] ; Amaral, Maria Marta ^[2] ; Sacerdoti, Flavia ^[2] ; Bernal, Alan Mauro ^[3] ; Quintilio, Wagner ^[4] ; Moro, Ana Maria ^[4] ; Palermo, Marina Sandra ^[3] ; Ibarra, Cristina ^[2] ; Fontes Piazza, Roxane Maria ^[1]

Affiliation

^[1] Inst Butantan, Lab Bacteriol, BR-05503900 Sao Paulo - Brazil

^[2] Univ Buenos Aires, Inst Fisiol & Biofis Bernardo Houssay IFIBIO Hous, CONICET, Lab Fisiopatogenia, Dept Fisiol, Fac Med, C1121, Buenos Aires, DF - Argentina

^[3] Acad Nacl Med Buenos Aires, CONICET, Inst Med Expt, Lab Patogenesis & Inmunol Proc Infecciosas, IMEX, C1425, Buenos Aires, DF - Argentina

^[4] Inst Butantan, Lab Biofarmacos Celulas Anim, BR-05503900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: TOXINS; v. 10, n. 12 DEC 2018.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 11/12928-2 - New challenge for the diagnosis of diarrheagenic Escherichia coli: recombinant antibody obtention against different virulence factors
• Grantee: Roxane Maria Fontes Piazza
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/17006-2 - Shiga toxin-producing Escherichia coli (STEC) intoxication and colonization in Zebrafish model: An in vivo alternative for pathogenicity studies and therapeutic antibodies validation
• Grantee: Daniela Luz Hessel da Cunha
• Support Opportunities: Scholarships in Brazil - Post-Doctoral