This project aims to identify and characterize human peptides inhibiting Bordetella pertussis toxin, which is the main virulence factor causing whooping cough. The applicant identified endogenous antimicrobial peptides of the defensin family, as well as angiogenin, as inhibitors of pertussis toxin. The project will define the underlying molecular and cellular mechanism(s). In addition, as-yet-unknown peptidic inhibitors will be identified from human peptide libraries. The results will elucidate the role of endogenous peptides as natural inhibitors against pertussis toxin and provide starting points for developing novel pharmacological approaches for the treatment of whooping cough.