Peptides derived from phage display libraries as potential neutralizers of Shiga toxin-induced cytotoxicity in vitro and in vivo.
OBJECTIVE
To use the phage display technique to develop peptides with the capability to neutralize the cytotoxicity induced by Stx1 and Stx2 toxins produced by Shiga toxin-producing Escherichia coli (STEC).


RESULTS
The phage display technique permitted the development of three peptides, named PC7-12, P12-26 and PC7-30, which bind to the globotriaosylceramide (Gb3) receptor for Shiga toxins produced by STEC. Moreover, these peptides were capable of competing efficiently with the Shiga toxins for binding to Gb3. The peptides described herein partially inhibited the Stx-induced cytotoxicity of cell-free filtrates of STEC O157 : H7 and purified Stx toxins in Vero cells. The inhibition of lethality induced by Stx toxins in mice indicated that peptide PC7-30 inhibited the lethality caused by Stx1 (2LD50) in mice.


CONCLUSIONS
The phage display technique permitted the development of peptides that inhibited the cytotoxicity induced by Stx toxins in vitro. Peptide PC7-30 inhibited the lethality of Stx1 in vivo; this molecule would be a promising candidate for the development of therapeutic agents for STEC-related diseases in humans.


CONCLUSIONS
The selection of Gb3, the common receptor for Stx1 and Stx2, may contribute to the development of efficient neutralizers for both toxins, and our approach would be an interesting alternative for the development of therapeutic molecules for the treatment of diseases caused by STEC strains.
Departamento de Genética, Evolução e Bioagentes, Instituto de Biologia-UNICAMP, Campinas, SP, Brazil.
R A
RA
Bernedo-Navarro
M M
MM
Miyachiro
M J
MJ
da Silva
C F
CF
Reis
R A
RA
Conceição
M S V
MS
Gatti
T
T
Yano
D000818:Animals; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D022622:Shiga Toxin 1 / Q000037:antagonists & inhibitors* / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors* / Q000633:toxicity; D054323:Shiga-Toxigenic Escherichia coli / Q000378:metabolism; D014281:Trihexosylceramides / Q000378:metabolism; D014709:Vero Cells
D019151:Peptide Library; D010455:Peptides; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D014281:Trihexosylceramides; C018549:globotriaosylceramide
EHEC (enterohaemorrhagic E. coli); bacteriophages; intestinal microbiology; peptides; toxins