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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 10, n. 12 DEC 2018.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 11/12928-2 - Novo desafio para o diagnóstico de Escherichia coli diarreiogênica: obtenção de anticorpos recombinantes contra diferentes fatores de virulência
• Beneficiário: Roxane Maria Fontes Piazza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/17006-2 - Intoxicação e colonização por Escherichia coli produtora da toxina de Shiga (STEC) em modelo de Zebrafish: uma alternativa para o estudo in vivo da patogenicidade e para validação de anticorpos terapêuticos.
• Beneficiário: Daniela Luz Hessel da Cunha
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado