Human peptides ��-defensin-1 and -5 inhibit pertussis toxin
| Autor: | Kling, Carolin, Pulliainen, Arto T., Barth, Holger, Ernst, Katharina |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
alpha-Defensins
antimicrobial peptide Bacterial toxins Whooping Cough Article Bordetella pertussis Defensins Anti-Infective Agents Animals Humans ddc:610 Virulence Factors Bordetella Child toxin inhibitor ADP-ribosylating toxin ADP-Ribosyltransferasen Defensine pertussis toxin ADP ribose transferases human peptide respiratory system Pore forming cytotoxic proteins bacterial AB-type toxin Medicine Bakteriengift DDC 610 / Medicine & health Antimicrobial Peptides |
| Zdroj: | Toxins, Vol 13, Iss 480, p 480 (2021) Toxins Volume 13 Issue 7 |
| DOI: | 10.18725/oparu-40041 |
| Popis: | Bordetella pertussis causes the severe childhood disease whooping cough, by releasing several toxins, including pertussis toxin (PT) as a major virulence factor. PT is an AB5-type toxin, and consists of the enzymatic A-subunit PTS1 and five B-subunits, which facilitate binding to cells and transport of PTS1 into the cytosol. PTS1 ADP-ribosylates ��-subunits of inhibitory G-proteins (G��i) in the cytosol, which leads to disturbed cAMP signaling. Since PT is crucial for causing severe courses of disease, our aim is to identify new inhibitors against PT, to provide starting points for novel therapeutic approaches. Here, we investigated the effect of human antimicrobial peptides of the defensin family on PT. We demonstrated that PTS1 enzyme activity in vitro was inhibited by ��-defensin-1 and -5, but not ��-defensin-1. The amount of ADP-ribosylated G��i was significantly reduced in PT-treated cells, in the presence of ��-defensin-1 and -5. Moreover, both ��-defensins decreased PT-mediated effects on cAMP signaling in the living cell-based interference in the G��i-mediated signal transduction (iGIST) assay. Taken together, we identified the human peptides ��-defensin-1 and -5 as inhibitors of PT activity, suggesting that these human peptides bear potential for developing novel therapeutic strategies against whooping cough. publishedVersion |
| Databáze: | OpenAIRE |
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