title: Sigma32-mediated negative regulation of Salmonella pathogenicity island 1 expression.
abstract: Salmonella pathogenicity island 1 (SPI1) enables infecting salmonellae to invade the intestinal epithelium and induce a proinflammatory response and macrophage cell death. SPI1 expression is controlled by a complex cascade with several transcriptional regulators within the island and global regulators outside it. Previously, we reported that DnaK-depleted salmonellae could neither invade epithelial cells nor secrete SPI1-encoded proteins, suggesting that DnaK is involved in the expression of SPI1. Here, we found that DnaK is involved in SPI1 expression through inhibition of sigma(32) protein, which directs the transcription of a group of genes in response to various global stresses. Overproduction of sigma(32) resulted in decreased levels of the SPI1-specific transcriptional regulators HilD and HilA. Further analysis demonstrated that the sigma(32)-mediated system negatively regulates HilD and HilA at the posttranslational and transcriptional levels, respectively. The executioner of this negative regulation was shown to be a sigma(32)-induced protein ATP-dependent Lon protease, which specifically degrades HilD. Since HilD can activate hilA transcription, is at the top of the hierarchical SPI1 regulatory loop, and has a dominant role, the posttranslational control of HilD by Lon is critically important for precise expression of SPI1. Consequently, we suggest that SPI1 expression is controlled by the feedback regulatory loop in which sigma(32) induces Lon to control turnover of HilD, and DnaK, which inhibits sigma(32) function, leading to the modulation of lon expression. This regulation in response to a specific combination of environmental signals would ensure that SPI1 expression is restricted to a few specific locations in the host.
authors: Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
authors: Mari
authors: M
authors: Matsui
authors: Akiko
authors: A
authors: Takaya
authors: Tomoko
authors: T
authors: Yamamoto
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D044404:Genomic Islands; D006360:Heat-Shock Proteins / Q000378:metabolism*; D049070:Protease La / Q000378:metabolism; D012486:Salmonella typhimurium / Q000502:physiology*; D012808:Sigma Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; C102236:HilA protein, Salmonella; C119660:HilD protein, Salmonella typhimurium; D012808:Sigma Factor; D015534:Trans-Activators; D014157:Transcription Factors; D037521:Virulence Factors; C069774:heat-shock sigma factor 32; D049070:Protease La