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

The control of innate immune responses through activation of the nuclear transcription factor NF-kappa 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-kappa B functions in activated mammalian cells. The consequence is specific repression of stimulus- mediated induction of NF-kappa B- 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.