Human alpha-defensins neutralize toxins of the mono-ADP-ribosyltransferase family |
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Authors: | Kim Chun Slavinskaya Zoya Merrill A Rod Kaufmann Stefan H E |
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Affiliation: | Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21-22, D-10117 Berlin, Germany. |
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Abstract: | Various bacterial pathogens secrete toxins, which are not only responsible for fatal pathogenesis of disease, but also facilitate evasion of host defences. One of the best-known bacterial toxin groups is the mono-ADP-ribosyltransferase family. In the present study, we demonstrate that human neutrophil alpha-defensins are potent inhibitors of the bacterial enzymes, particularly against DT (diphtheria toxin) and ETA (Pseudomonas exotoxin A). HNP1 (human neutrophil protein 1) inhibited DT- or ETA-mediated ADP-ribosylation of eEF2 (eukaryotic elongation factor 2) and protected HeLa cells against DT- or ETA-induced cell death. Kinetic analysis revealed that inhibition of DT and ETA by HNP1 was competitive with respect to eEF2 and uncompetitive against NAD+ substrates. Our results reveal that toxin neutralization represents a novel biological function of HNPs in host defence. |
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