The curli regulator CsgD mediates stationary phase counter-silencing of csgBA in Salmonella Typhimurium.

Integration of horizontally acquired genes into transcriptional networks is essential for the regulated expression of virulence in bacterial pathogens. In Salmonella enterica, expression of such genes is repressed by the nucleoid-associated protein H-NS, which recognizes and binds to AT-rich DNA. H-NS-mediated silencing must be countered by other DNA-binding proteins to allow expression under appropriate conditions. Some genes that can be transcribed by RNA polymerase (RNAP) associated with the alternative sigma factor σ(S) or the housekeeping sigma factor σ(70) in vitro appear to be preferentially transcribed by σ(S) in the presence of H-NS, suggesting that σ(S) may act as a counter-silencer. To determine whether σ(S) directly counters H-NS-mediated silencing and whether co-regulation by H-NS accounts for the σ(S) selectivity of certain promoters, we examined the csgBA operon, which is required for curli fimbriae expression and is known to be regulated by both H-NS and σ(S) . Using genetics and in vitro biochemical analyses, we found that σ(S) is not directly required for csgBA transcription, but rather up-regulates csgBA via an indirect upstream mechanism. Instead, the biofilm master regulator CsgD directly counter-silences the csgBA promoter by altering the DNA-protein complex structure to disrupt H-NS-mediated silencing in addition to directing the binding of RNAP.