Characterization of SprA, an AraC-like transcriptional regulator encoded within the Salmonella typhimurium pathogenicity island 1

Pathogenicity island 1 (SPI-1) located at centisome 63 of the Salmonella ch romosome encodes a type III protein secretion system that is essential for its pathogenicity. The translocation of effector proteins through this syst em results in the stimulation of signalling events, leading to actin cytosk eletal rearrangements and nuclear responses. These cellular responses ultim ately lead to bacterial uptake, production of proinflammatory cytokines in non-phagocytic cells and the initiation of programmed cell death in macroph ages. The regulation of expression of components and substrates of this typ e III secretion system is complex and involves the activity of several spec ific transcriptional regulatory proteins encoded within SPI-1, Here, we des cribe two additional regulatory proteins, Spl A and SprB, which are encoded within SPI-1. SprA and SprB exhibit significant sequence similarity to the AraC/XylS and the LuxR/UhaP family of transcriptional regulatory proteins respectively. Insertion mutations in sprA and sprB did not significantly af fect the transcription of invasion-associated genes and, consequently, did not affect the ability of Salmonella typhimurium to gain access into host c ells. However, expression of sprA from an inducible heterologous promoter r esulted in increased expression of genes associated with the centisome 63 t ype III secretion system and increased the ability of S. typhimurium to ent er into host cells. Further analysis demonstrated that SprA acts either ups tream or at the same level as HilA in the SPI-1 transcriptional regulatory cascade.