Regulation of the Salmonella Pathogenicity Island 1 Type Three Secretion System
Ellermeier, Jeremy R.
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Permalink
https://hdl.handle.net/2142/86705
Description
Title
Regulation of the Salmonella Pathogenicity Island 1 Type Three Secretion System
Author(s)
Ellermeier, Jeremy R.
Issue Date
2008
Doctoral Committee Chair(s)
Slauch, James M.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Microbiology
Language
eng
Abstract
"The invasion of intestinal epithelial cells by Salmonella enterica serovar Typhimurium is mediated by a Type Three Secretion System (T3SS) encoded on Salmonella pathogenicity island 1 (SPI1). The SPI1 TTSS injects effector proteins into the cytosol of host cells where they promote actin rearrangement and engulfment of the bacteria. HilC, HilD, and RtsA activate expression of SPI1 genes by binding upstream of the master regulatory gene hilA to induce its expression. HilA activates the SPI1 T3SS structural genes. Here I present evidence that hilA expression, and hence the SPI1 T3SS, is controlled by a feedforward regulatory loop. I demonstrate that HilC, HilD, and RtsA are each capable of independently inducing expression of the hilC, hilD, and rtsA genes, and that each can independently activate hilA. Using competition assays in vivo, I show that each of the hilA regulators contribute to SPI1 induction in the intestine. Of the three, HilD has a predominant role, but apparently does not act alone either in vivo or in vitro to sufficiently activate SPI1. The two-component regulatory systems, SirA/BarA and OmpR/EnvZ, function through Hi1D, thus inducing hilC, rtsA, and hilA. However, the two-component systems are not responsible for environmental regulation of SPI1. Rather, ""SPI1 inducing conditions"" cause independent activation of the rtsA, hilC, and hilD genes in the absence of known regulators. One potential environmental signal is iron. Fur controls the iron response in the cell and activates hilA transcription in a HilD-dependent manner. Fur regulation of HilD does not appear to be simply at the transcriptional or translational level, but rather requires the presence of HilD protein. Fur activation of SPI1 is not mediated through the Fur regulated small RNAs, RfrA and RfrB, which are the Salmonella ortholog and paralog of RyhB (RfrA and RfrB, respectively) that control expression of sodB. The PhoP/PhoQ two-component regulatory system represses expression of SPI1 genes. This system works independently of HilD protein by negatively regulating hilA expression directly at the hilA promoter. Additionally, fatty acid degradation plays an undefined role in the regulation of SPI1. Although the exact mechanism of regulation for some of these factors is still unknown, and there is still much work to be done, this work provides a key step in understanding the SPI1 T3SS regulatory circuit."
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