SHIGELLA-FLEXNERI INVASION OF HELA-CELLS INDUCES NF-KAPPA-B DNA-BINDING ACTIVITY

Although information about the genetic basis and mechanisms of Shigell a flexneri cellular invasion is accumulating, little is known about ch anges in cell signaling and their consequences following bacterium-hos t cell interactions. A general result of signal transduction is altera tions in the levels and/or activities of transcription factors. Altera tions in transcription factor binding activities were observed followi ng challenge with S. flexneri. Changes in the DNA-binding activities o f cellular transcription factors to AP1, AP2, cyclic AMP response elem ent, CTF1/NF1, NF-kappaB/Rel, OCT1, and SP1 DNA-binding sites were inv estigated by electrophoretic mobility shift assays. NF-kappaB/Rel DNA- binding activity was enhanced more than 11-fold by cellular invasion; noninvasive S. flexneri strains induced low levels of kappaB DNA bindi ng. Both subunits of the NF-kappaB transcription factor, p50 and p65, but not c-Rel (p85), are components of the kappaB DNA-binding activity . These data suggest that changes in cellular transcription factor bin ding activity are a consequence of S. flexneri invasion, and these cha nges could play a role in the initial host response or in the pathogen esis of the disease.