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Article

Human Peptides α-Defensin-1 and -5 Inhibit Pertussis Toxin

1
Institute of Pharmacology and Toxicology, Ulm University Medical Center, 89081 Ulm, Germany
2
Institute of Biomedicine, Research Unit for Infection and Immunity, University of Turku, FI-20520 Turku, Finland
*
Author to whom correspondence should be addressed.
Toxins 2021, 13(7), 480; https://doi.org/10.3390/toxins13070480
Received: 14 June 2021 / Revised: 1 July 2021 / Accepted: 9 July 2021 / Published: 11 July 2021
(This article belongs to the Special Issue Pertussis Toxin and Research on Pertussis Vaccine)
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 α-subunits of inhibitory G-proteins (Gαi) 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 α-defensin-1 and -5, but not β-defensin-1. The amount of ADP-ribosylated Gαi was significantly reduced in PT-treated cells, in the presence of α-defensin-1 and -5. Moreover, both α-defensins decreased PT-mediated effects on cAMP signaling in the living cell-based interference in the Gαi-mediated signal transduction (iGIST) assay. Taken together, we identified the human peptides α-defensin-1 and -5 as inhibitors of PT activity, suggesting that these human peptides bear potential for developing novel therapeutic strategies against whooping cough. View Full-Text
Keywords: pertussis toxin; defensins; ADP-ribosylating toxin; bacterial AB-type toxin; human peptide; antimicrobial peptide; toxin inhibitor pertussis toxin; defensins; ADP-ribosylating toxin; bacterial AB-type toxin; human peptide; antimicrobial peptide; toxin inhibitor
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MDPI and ACS Style

Kling, C.; Pulliainen, A.T.; Barth, H.; Ernst, K. Human Peptides α-Defensin-1 and -5 Inhibit Pertussis Toxin. Toxins 2021, 13, 480. https://doi.org/10.3390/toxins13070480

AMA Style

Kling C, Pulliainen AT, Barth H, Ernst K. Human Peptides α-Defensin-1 and -5 Inhibit Pertussis Toxin. Toxins. 2021; 13(7):480. https://doi.org/10.3390/toxins13070480

Chicago/Turabian Style

Kling, Carolin, Arto T. Pulliainen, Holger Barth, and Katharina Ernst. 2021. "Human Peptides α-Defensin-1 and -5 Inhibit Pertussis Toxin" Toxins 13, no. 7: 480. https://doi.org/10.3390/toxins13070480

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