Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences

Chun Kim; Nadesan Gajendran; Hans Willi Mittrücker; Matthias Weiwad; Young Hwa Song; Robert Hurwitz; Matthias Wilmanns; Gunter Fischer; Stefan H.E. Kaufmann

doi:10.1073/pnas.0500508102

Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences

Chun Kim, Nadesan Gajendran, Hans Willi Mittrücker, Matthias Weiwad, Young Hwa Song, Robert Hurwitz, Matthias Wilmanns, Gunter Fischer, Stefan H.E. Kaufmann^*

^*Corresponding author for this work

Institute of Physics

119 Citations (Scopus)

Abstract

Anthrax caused by Bacillus anthracis represents a major bioterroristic threat. B. anthracis produces lethal toxin (LeTx), a combination of lethal factor (LF) and protective antigen that plays a major role in anthrax pathogenesis. We demonstrate that human neutrophil α-defensins are potent inhibitors of LF. The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive. HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in LeTx-treated macrophages. HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx.

Original language	English
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	13
Pages (from-to)	4830-4835
Number of pages	6
ISSN	0027-8424
DOIs	https://doi.org/10.1073/pnas.0500508102
Publication status	Published - 29.03.2005

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10.1073/pnas.0500508102

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Kim, C., Gajendran, N., Mittrücker, H. W., Weiwad, M., Song, Y. H., Hurwitz, R., Wilmanns, M., Fischer, G., & Kaufmann, S. H. E. (2005). Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proceedings of the National Academy of Sciences of the United States of America, 102(13), 4830-4835. https://doi.org/10.1073/pnas.0500508102

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title = "Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences",

abstract = "Anthrax caused by Bacillus anthracis represents a major bioterroristic threat. B. anthracis produces lethal toxin (LeTx), a combination of lethal factor (LF) and protective antigen that plays a major role in anthrax pathogenesis. We demonstrate that human neutrophil α-defensins are potent inhibitors of LF. The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive. HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in LeTx-treated macrophages. HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx.",

author = "Chun Kim and Nadesan Gajendran and Mittr{\"u}cker, {Hans Willi} and Matthias Weiwad and Song, {Young Hwa} and Robert Hurwitz and Matthias Wilmanns and Gunter Fischer and Kaufmann, {Stefan H.E.}",

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doi = "10.1073/pnas.0500508102",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. / Kim, Chun; Gajendran, Nadesan; Mittrücker, Hans Willi et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 13, 29.03.2005, p. 4830-4835.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences

AU - Kim, Chun

AU - Gajendran, Nadesan

AU - Mittrücker, Hans Willi

AU - Weiwad, Matthias

AU - Song, Young Hwa

AU - Hurwitz, Robert

AU - Wilmanns, Matthias

AU - Fischer, Gunter

AU - Kaufmann, Stefan H.E.

PY - 2005/3/29

Y1 - 2005/3/29

N2 - Anthrax caused by Bacillus anthracis represents a major bioterroristic threat. B. anthracis produces lethal toxin (LeTx), a combination of lethal factor (LF) and protective antigen that plays a major role in anthrax pathogenesis. We demonstrate that human neutrophil α-defensins are potent inhibitors of LF. The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive. HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in LeTx-treated macrophages. HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx.

AB - Anthrax caused by Bacillus anthracis represents a major bioterroristic threat. B. anthracis produces lethal toxin (LeTx), a combination of lethal factor (LF) and protective antigen that plays a major role in anthrax pathogenesis. We demonstrate that human neutrophil α-defensins are potent inhibitors of LF. The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive. HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in LeTx-treated macrophages. HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx.

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U2 - 10.1073/pnas.0500508102

DO - 10.1073/pnas.0500508102

M3 - Journal articles

C2 - 15772169

AN - SCOPUS:16344366178

SN - 0027-8424

VL - 102

SP - 4830

EP - 4835

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 13

ER -

Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences

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