title: Human alpha-defensins neutralize toxins of the mono-ADP-ribosyltransferase family.
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.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21-22, D-10117 Berlin, Germany.
authors.forename: Chun
authors.initials: C
authors.lastname: Kim
authors.forename: Zoya
authors.initials: Z
authors.lastname: Slavinskaya
authors.forename: A Rod
authors.initials: AR
authors.lastname: Merrill
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D003353:Corynebacterium diphtheriae / Q000502:physiology; D004167:Diphtheria Toxin / Q000378:metabolism*; D005098:Exotoxins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D009243:NAD / Q000378:metabolism; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D011485:Protein Binding; D013379:Substrate Specificity; D013816:Thermodynamics; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: D004167:Diphtheria Toxin; D005098:Exotoxins; D020652:Peptide Elongation Factor 2; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D009243:NAD; D000246:Adenosine Diphosphate Ribose