Two AraC/XylS family members can independently counteract the effect of repressing sequences upstream of the hilA promoter.
During infection of its hosts, Salmonella enterica serovar Typhimurium (S. typhimurium) enters the epithelial cells of the small intestine. This process requires a number of invasion genes encoded on Salmonella pathogenicity island 1 (SPI1), a 40 kb stretch of DNA located near minute 63 of the S. typhimurium chromosome. Expression of S. typhimurium SPI1 invasion genes is activated by the transcription factor HilA. hilA is tightly regulated in response to many environmental conditions, including oxygen, osmolarity and pH. Regulation of hilA expression may serve to limit invasion gene expression to the appropriate times during Salmonella infection. We have mapped the transcription start site of hilA and identified regions of the promoter that are required for the repression of hilA expression by conditions unfavourable for Salmonella invasion. We have also identified two SPI1-encoded genes, hilC and hilD, that can independently derepress hilA expression. HilC and HilD are both members of the AraC/XylS family of transcriptional regulators. A mutation in hilD significantly reduces the ability of S. typhimurium to enter tissue culture cells, whereas a mutation in hilC only modestly affects Salmonella invasion. Based on these results, we have updated our model of Salmonella SPI1 invasion gene regulation. We also speculate on the possible significance of this model for Salmonella pathogenesis.
D051777:AraC Transcription Factor; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D004268:DNA-Binding Proteins; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic