{"doi":"10.1016/j.jbc.2024.107950","title":"Alpha-1 antitrypsin inhibits pertussis toxin","abstract":"Pertussis (whooping cough) is a vaccine-preventable but re-emerging, highly infectious respiratory disease caused by Bordetella pertussis . There are currently no effective treatments for pertussis, complicating care for nonvaccinated individuals, especially newborns. Disease manifestations are predominantly caused by pertussis toxin (PT), a pivotal virulence factor classified as an ADP-ribosylating AB-type protein toxin. In this work, an unbiased approach using peptide libraries, bioassay-guided fractionation and mass spectrometry revealed α 1 -antitrypsin (α 1 AT) as a potent PT inhibitor. Biochemistry-, cell culture-, and molecular modeling-based in vitro experimentation demonstrated that the α 1 AT mode of action is based on blocking PT-binding to the host target cell surface. In the infant mouse model of severe pertussis, α 1 AT expression was reduced upon infection. Further, systemic administration of α 1 AT significantly reduced B. pertussis- induced leukocytosis, which is a hallmark of infant infection and major risk factor for fatal pertussis. Taken together our data demonstrates that α 1 AT is a novel PT inhibitor and that further evaluation and development of α 1 AT as a therapeutic agent for pertussis is warranted. Importantly, purified α 1 AT is already in use clinically as an intravenous augmentation therapy for those with genetic α 1 AT deficiency and could be repurposed to clinical management of pertussis.","journal":"Journal of Biological Chemistry","year":2024,"id":443581,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9659,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1258794,"name":"Anja Sommer","orcid":null,"position":1,"is_corresponding":false},{"id":1258795,"name":"Lena-Marie Sokolowski","orcid":null,"position":2,"is_corresponding":false},{"id":1258796,"name":"Carolin Kling","orcid":null,"position":3,"is_corresponding":false},{"id":568448,"name":"Armando Rodríguez","orcid":"0000-0001-5921-3770","position":4,"is_corresponding":false},{"id":569293,"name":"Nico Preising","orcid":null,"position":5,"is_corresponding":false},{"id":1258195,"name":"Daniel Alpízar-Pedraza","orcid":"0000-0002-0281-680X","position":6,"is_corresponding":false},{"id":1258797,"name":"Jaylyn King","orcid":null,"position":7,"is_corresponding":false},{"id":1258196,"name":"Lisa Streit","orcid":"0000-0002-1878-5665","position":8,"is_corresponding":false},{"id":408046,"name":"Bernd Schröppel","orcid":null,"position":9,"is_corresponding":false},{"id":1258798,"name":"R. van Erp","orcid":null,"position":10,"is_corresponding":false},{"id":1258799,"name":"Eberhard Barth","orcid":null,"position":11,"is_corresponding":false},{"id":1258800,"name":"Marion Schneider","orcid":null,"position":12,"is_corresponding":false},{"id":568454,"name":"Jan Münch","orcid":"0000-0001-7316-7141","position":13,"is_corresponding":false},{"id":618730,"name":"Jens Michaelis","orcid":"0000-0002-2739-4172","position":14,"is_corresponding":false},{"id":569294,"name":"Ludger Ständker","orcid":null,"position":15,"is_corresponding":false},{"id":172893,"name":"Sebastian Wiese","orcid":"0000-0001-5697-2608","position":16,"is_corresponding":false},{"id":1258197,"name":"Holger Barth","orcid":"0000-0002-2706-3402","position":17,"is_corresponding":false},{"id":325192,"name":"Arto T. Pulliainen","orcid":"0000-0002-9361-8963","position":18,"is_corresponding":false},{"id":548604,"name":"Karen M. Scanlon","orcid":"0000-0002-5300-8749","position":19,"is_corresponding":false},{"id":1258198,"name":"Katharina Ernst","orcid":"0000-0002-9832-9917","position":20,"is_corresponding":false},{"id":1258793,"name":"Stefanie Lietz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39481600","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}