Targeting toxins to treat whooping cough

Whooping cough is an infectious respiratory disease caused by the bacteria Bordetella pertussis. According to the U.S. Centers for Disease Control and Prevention, whooping cough cases are rising. While early antibiotic treatment can be effective, most diagnoses do not occur until after this therapeutic window has passed.

Whooping cough bacteria

In a recent Journal of Biological Chemistry article , Stefanie Lietz from Ulm University, Germany, and an international team explored the human peptidome — the complete collection of peptides in the human body — for pertussis toxin, or PT, inhibitors using peptide libraries, fractionation and mass spectrometry. They identified the liver protein α1-antitrypsin, or α1AT, as a potent PT inhibitor. Additional cell culture and molecular modeling experiments indicated that α1AT likely binds to PT in solution and thus blocks the toxin from making contact with its known host glycoprotein cell surface interaction partner for endocytosis.

Patients with genetic α1AT deficiency receive synthetic α1AT in the clinic. Therefore, α1AT may be able to be repurposed to treat PT-mediated pertussis pathogenesis. Future studies will fill in details about α1AT’s mechanism of action against PT, such as verifying the α1AT residues involved in binding PT.