Human {alpha}-defensins neutralize toxins of the mono-ADP-ribosyltransferase family

Chun Kim , Zoya Slavinskaya , A. Rod Merrill , Stefan H.E. Kaufmann (1)

1 Department of Immunology [MPIIB Berlin]

Various bacterial pathogens secrete toxins, which are not only responsible for fatal pathogenesis of disease, but also facilitate evasion from host defenses. One of the best known bacterial toxin groups is the mono-ADP-ribosyltransferase family. Here, we demonstrate that human neutrophil {alpha}-defensins are potent inhibitors of the bacterial enzymes, particularly against diphtheria toxin (DT) and Pseudomonas exotoxin A (ETA). Human neutrophil protein 1 (HNP1) inhibited DT- or ETA-mediated ADP-ribosylation of eukaryotic elongation factor 2 (eEF2) 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 data reveal that toxin neutralization represents a novel biological function of HNPs in host defense.

Mots clés: Life Sciences

Chun Kim, Zoya Slavinskaya, A. Rod Merrill, Stefan H.E. Kaufmann. Human {alpha}-defensins neutralize toxins of the mono-ADP-ribosyltransferase family. Biochemical Journal, 2006, 399 (2), pp.225-229. ⟨10.1042/BJ20060425⟩. ⟨hal-00478559⟩