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 α-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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Research Article|
September 27 2006
Human α-defensins neutralize toxins of the mono-ADP-ribosyltransferase family
Chun Kim;
Chun Kim
1
*Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21-22, D-10117 Berlin, Germany
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Zoya Slavinskaya;
Zoya Slavinskaya
†Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada N1G 2W1
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A. Rod Merrill;
A. Rod Merrill
†Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada N1G 2W1
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Stefan H. E. Kaufmann
Stefan H. E. Kaufmann
2
*Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21-22, D-10117 Berlin, Germany
2To whom correspondence should be addressed (email kaufmann@mpiib-berlin.mpg.de).
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Publisher: Portland Press Ltd
Received:
March 20 2006
Revision Received:
June 16 2006
Accepted:
July 03 2006
Accepted Manuscript online:
July 03 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 399 (2): 225–229.
Article history
Received:
March 20 2006
Revision Received:
June 16 2006
Accepted:
July 03 2006
Accepted Manuscript online:
July 03 2006
Citation
Chun Kim, Zoya Slavinskaya, A. Rod Merrill, Stefan H. E. Kaufmann; Human α-defensins neutralize toxins of the mono-ADP-ribosyltransferase family. Biochem J 15 October 2006; 399 (2): 225–229. doi: https://doi.org/10.1042/BJ20060425
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