Modulation of gene expression via disruption of NF-kappaB signaling by a bacterial small molecule.
Kravchenko VV, Kaufmann GF, Mathison JC, Scott DA, Katz AZ, Grauer DC, Lehmann M, Meijler MM, Janda KD, Ulevitch RJ.
The control of innate immune responses through activation of the nuclear transcription factor NF-kappaB 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-kappaB functions in activated mammalian cells. The consequence is specific repression of stimulus-mediated induction of NF-kappaB-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.