Shigella flexneri invasion of HeLa cells induces NF-κB DNA-binding activity

Although information about the genetic basis and mechanisms of Shigella flexneri cellular invasion is accumulating, little is known about changes in cell signaling and their consequences following bacterium-host cell interactions. A general result of signal transduction is alterations in the levels and/or activities of transcription factors. Alterations in transcription factor binding activities were observed following challenge with S. flexneri. Changes in the DNA-binding activities of cellular transcription factors to AP1, AP2, cyclic AMP response element, CTF1/NF1, NF- κB/Rel, OCT1, and SP1 DNA-binding sites were investigated by electrophoretic mobility shift assays. NF-κB/Rel DNA-binding activity was enhanced more than 11-fold by cellular invasion; noninvasive S. flexneri strains induced low levels of κB DNA binding. Both subunits of the NF-κB transcription factor, p50 and p65, but not c-Rel (p85), are components of the κB DNA-binding activity. These data suggest that changes in cellular transcription factor binding activity are a consequence of S. flexneri invasion, and these changes could play a role in the initial host response or in the pathogenesis of the disease.