title: AraC/XylS family members, HilD and HilC, directly activate virulence gene expression independently of HilA in Salmonella typhimurium.
abstract: Salmonella typhimurium is a Gram-negative enteric pathogen that can infect intestinal epithelial cells and induce inflammation of the intestinal mucosa. These processes are mediated by a type III secretion system (TTSS), which is encoded on Salmonella pathogenicity island 1 (SPI1). Previous studies showed that four SPI1-encoded transcriptional regulators, HilD, HilC, HilA and InvF, act in an ordered fashion to co-ordinately activate expression of the SPI1 TTSS. HilD and HilC derepress hilA transcription. HilA activates invF as well as SPI1 genes that encode components of the TTS apparatus. InvF then activates genes that encode proteins secreted by the SPI1 TTS apparatus. In this scheme, HilD and HilC indirectly activate expression of the SPI1 TTS apparatus and its secreted substrates by affecting hilA expression. Here, we report that HilD and HilC can also activate expression of a subset of SPI1 genes independently of HilA. Our studies show that HilD and HilC activate transcription of invF from a promoter that is far upstream of its HilA-dependent promoter. This activation is most probably through direct binding of HilD and HilC to sequences upstream and downstream of this alternative HilA-independent promoter. We conclude that HilD and HilC have a second role in SPI1 gene regulation that is separate from their role in co-ordinating expression of the SPI1 TTSS through hilA.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Samina
authors.initials: S
authors.lastname: Akbar
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Schechter
authors.forename: C Phoebe
authors.initials: CP
authors.lastname: Lostroh
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Lee
mesh_terms: D051777:AraC Transcription Factor; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015964:Gene Expression Regulation, Bacterial; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000145:classification / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015534:Trans-Activators / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
chemical_list: D051777:AraC Transcription Factor; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C102236:HilA protein, Salmonella; C119659:HilC protein, Salmonella typhimurium; C119660:HilD protein, Salmonella typhimurium; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C078720:XylS protein, Pseudomonas putida; C090990:invF protein, Salmonella