Screening and identification of receptor antagonist for shiga toxin from random peptides displayed on filamentous bacteriophages

The bacteriophage clones which can bind with shiga toxin B subunit (StxB) a nd inhibit cytotoxicity of shiga toxin were obtained by using antibody capt uring method from a 15-mer random peptide library displayed on the surface of bacteriophage fd. Among them, one peptide encoded by the random DNA regi on of a selected bacteriophage (A12) was synthesized and tested in vitro an d in vivo, where the peptide competed with the receptor of shiga toxin to b ind StxB, and inhibited the cytotoxicity and enterotoxicity of shiga toxin. The peptide can also block other apparently unrelated StxB binding bacteri ophage (A3), which suggests that there are overlapping StxB interaction sit es for these ligands with different sequences. The results provide a demons tration of bacteriophage display to screen peptide ligands for a small and/ or unable biotinylated molecule by antibodies-capturing strategy, and take the lead for the development of receptor antagonists for shiga toxin.