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.