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Modulation of Gene Expression via Disruption of NF-B Signaling by a Bacterial Small Molecule
Vladimir V. Kravchenko,1Gunnar F. Kaufmann,1,2,3John C. Mathison,1David A. Scott,1Alexander Z. Katz,1David C. Grauer,1Mandy Lehmann,1Michael M. Meijler,1,2,3*Kim D. Janda,1,2,3,4Richard J. Ulevitch1
The control of innate immune responses through activation ofthe nuclear transcription factor NF-B is essential for the eliminationof invading microbial pathogens. We showed that the bacterialN-(3-oxo-dodecanoyl) homoserine lactone (C12) selectively impairsthe regulation of NF-B functions in activated mammalian cells.The consequence is specific repression of stimulus-mediatedinduction of NF-B–responsive genes encoding inflammatorycytokines and other immune regulators. These findings uncovera strategy by which C12-producing opportunistic pathogens, suchas Pseudomonas aeruginosa, attenuate the innate immune systemto establish and maintain local persistent infection in humans,for example, in cystic fibrosis patients.
1 Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 2 Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 3 The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 4 Worm Institute of Research and Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA92037, USA.
* Present address: Department of Chemistry, Ben-Gurion Universityof Negev, Be'er Sheva, Israel.
To whom correspondence should be addressed. E-mail: ulevitch{at}scripps.edu
Pseudomonas aeruginosa Inhibition of Flagellin-Activated NF-{kappa}B and Interleukin-8 by Human Airway Epithelial Cells.
J. Pena, Z. Fu, C. Schwarzer, and T. E. Machen (2009)
Infect. Immun.
77, 2857-2865
|Abstract »|Full Text »|PDF »
Genome-Wide Innate Immune Responses in HIV-1-Infected Macrophages Are Preserved Despite Attenuation of the NF-{kappa}B Activation Pathway.
M. Noursadeghi, J. Tsang, R. F. Miller, S. Straschewski, P. Kellam, B. M. Chain, and D. R. Katz (2009)
J. Immunol.
182, 319-328
|Abstract »|Full Text »|PDF »
B Signaling by a Bacterial Small Molecule
B 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-
To whom correspondence should be addressed. E-mail: 
