Human alpha-defensins neutralize toxins of the mono-ADP-ribosyltransferase family.
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.
Kim
Chun
C
Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21-22, D-10117 Berlin, Germany.
Slavinskaya
Zoya
Z
Merrill
A Rod
AR
Kaufmann
Stefan H E
SH
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*
D004167:Diphtheria Toxin; D005098:Exotoxins; D020652:Peptide Elongation Factor 2; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D009243:NAD; D000246:Adenosine Diphosphate Ribose