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Peptides derived from phage display libraries as potential neutralizers of Shiga toxin‐induced cytotoxicity in vitro and in vivo
Author(s) -
BernedoNavarro R.A.,
Miyachiro M.M.,
Silva M.J.,
Reis C.F.,
Conceição R.A.,
Gatti M.S.V.,
Yano T.
Publication year - 2014
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/jam.12451
Subject(s) - in vivo , cytotoxicity , in vitro , phage display , microbiology and biotechnology , shiga toxin , toxin , microbial toxins , chemistry , biology , escherichia coli , biochemistry , genetics , peptide , gene
Aims To use the phage display technique to develop peptides with the capability to neutralize the cytotoxicity induced by S tx1 and S tx2 toxins produced by S higa toxin‐producing E scherichia coli ( STEC ). Methods and Results The phage display technique permitted the development of three peptides, named PC 7–12, P 12–26 and PC 7–30, which bind to the globotriaosylceramide ( G b3) receptor for Shiga toxins produced by STEC . Moreover, these peptides were capable of competing efficiently with the S higa toxins for binding to G b3. The peptides described herein partially inhibited the S tx‐induced cytotoxicity of cell‐free filtrates of STEC O 157 : H 7 and purified S tx toxins in Vero cells. The inhibition of lethality induced by S tx toxins in mice indicated that peptide PC 7–30 inhibited the lethality caused by S tx1 (2 LD 50 ) in mice. Conclusions The phage display technique permitted the development of peptides that inhibited the cytotoxicity induced by S tx toxins in vitro . Peptide PC 7–30 inhibited the lethality of S tx1 in vivo ; this molecule would be a promising candidate for the development of therapeutic agents for STEC ‐related diseases in humans. Significance and Impact of the Study The selection of G b3, the common receptor for S tx1 and S tx2, 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.