Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule

Vladimir V. Kravchenko; Gunnar F. Kaufmann; John C. Mathison; David A. Scott; Alexander Z. Katz; David C. Grauer; Mandy Lehmann; Michael M. Meijler; Kim D. Janda; Richard J. Ulevitch

doi:10.1126/science.1156499

Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule

Vladimir V. Kravchenko, Gunnar F. Kaufmann, John C. Mathison, David A. Scott, Alexander Z. Katz, David C. Grauer, Mandy Lehmann, Michael M. Meijler, Kim D. Janda, Richard J. Ulevitch

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

179 Scopus citations

Abstract

The control of innate immune responses through activation of the nuclear transcription factor NF-κB is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairs the regulation of NF-κB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-κB-responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12-producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.

Original language	English
Pages (from-to)	259-263
Number of pages	5
Journal	Science
Volume	321
Issue number	5886
DOIs	https://doi.org/10.1126/science.1156499
State	Published - 11 Jul 2008

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title = "Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule",

abstract = "The control of innate immune responses through activation of the nuclear transcription factor NF-κB is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairs the regulation of NF-κB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-κB-responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12-producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.",

author = "Kravchenko, {Vladimir V.} and Kaufmann, {Gunnar F.} and Mathison, {John C.} and Scott, {David A.} and Katz, {Alexander Z.} and Grauer, {David C.} and Mandy Lehmann and Meijler, {Michael M.} and Janda, {Kim D.} and Ulevitch, {Richard J.}",

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T1 - Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule

AU - Kravchenko, Vladimir V.

AU - Kaufmann, Gunnar F.

AU - Mathison, John C.

AU - Scott, David A.

AU - Katz, Alexander Z.

AU - Grauer, David C.

AU - Lehmann, Mandy

AU - Meijler, Michael M.

AU - Janda, Kim D.

AU - Ulevitch, Richard J.

PY - 2008/7/11

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N2 - The control of innate immune responses through activation of the nuclear transcription factor NF-κB is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairs the regulation of NF-κB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-κB-responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12-producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.

AB - The control of innate immune responses through activation of the nuclear transcription factor NF-κB is essential for the elimination of invading microbial pathogens. We showed that the bacterial N-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairs the regulation of NF-κB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-κB-responsive genes encoding inflammatory cytokines and other immune regulators. These findings uncover a strategy by which C12-producing opportunistic pathogens, such as Pseudomonas aeruginosa, attenuate the innate immune system to establish and maintain local persistent infection in humans, for example, in cystic fibrosis patients.

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Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule

Abstract

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