Selwan Hamed1,2, Riham M Shawky3, Mohamed Emara3, James M Slauch4, Christopher V Rao5. 1. Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave, Urbana, IL, 61801, USA. silwan_mustafa@pharm.helwan.edu.eg. 2. Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University - Ain Helwan, Helwan, 11795, Egypt. silwan_mustafa@pharm.helwan.edu.eg. 3. Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University - Ain Helwan, Helwan, 11795, Egypt. 4. Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. 5. Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave, Urbana, IL, 61801, USA. cvrao@illinois.edu.
Abstract
BACKGROUND: Salmonella enterica serovar Typhimurium is an intestinal pathogen capable of infecting a wide range of animals. It initiates infection by invading intestinal epithelial cells using a type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). The SPI-1 genes are regulated by multiple interacting transcription factors. The master regulator is HilD. HilE represses SPI-1 gene expression by binding HilD and preventing it from activating its target promoters. Previous work found that acetate and nutrients synergistically induce SPI-1 gene expression. In the present study, we investigated the role of HilE, nominally a repressor of SPI-1 gene expression, in mediating this response to acetate and nutrients. RESULTS: HilE is necessary for activation of SPI-1 gene expression by acetate and nutrients. In mutants lacking hilE, acetate and nutrients no longer increase SPI-1 gene expression but rather repress it. This puzzling response is not due to the BarA/SirA two component system, which governs the response to acetate. To identify the mechanism, we profiled gene expression using RNAseq in the wild type and a ΔhilE mutant under different growth conditions. Analysis of these data suggested that the Rcs system, which regulates gene expression in response to envelope stress, is involved. Consistent with this hypothesis, acetate and nutrients were able to induce SPI-1 gene expression in mutants lacking hilE and the Rcs system. CONCLUSIONS: While the exact mechanism is unknown, these results demonstrate the HilE, nominally a repressor of SPI-1 gene expression, can also function as an activator under the growth conditions investigated. Collectively, these results provide new insights regarding SPI-1 gene regulation and demonstrate that HilE is more complex than initially envisioned.
BACKGROUND:Salmonella enterica serovar Typhimurium is an intestinal pathogen capable of infecting a wide range of animals. It initiates infection by invading intestinal epithelial cells using a type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). The SPI-1 genes are regulated by multiple interacting transcription factors. The master regulator is HilD. HilE represses SPI-1 gene expression by binding HilD and preventing it from activating its target promoters. Previous work found that acetate and nutrients synergistically induce SPI-1 gene expression. In the present study, we investigated the role of HilE, nominally a repressor of SPI-1 gene expression, in mediating this response to acetate and nutrients. RESULTS: HilE is necessary for activation of SPI-1 gene expression by acetate and nutrients. In mutants lacking hilE, acetate and nutrients no longer increase SPI-1 gene expression but rather repress it. This puzzling response is not due to the BarA/SirA two component system, which governs the response to acetate. To identify the mechanism, we profiled gene expression using RNAseq in the wild type and a ΔhilE mutant under different growth conditions. Analysis of these data suggested that the Rcs system, which regulates gene expression in response to envelope stress, is involved. Consistent with this hypothesis, acetate and nutrients were able to induce SPI-1 gene expression in mutants lacking hilE and the Rcs system. CONCLUSIONS: While the exact mechanism is unknown, these results demonstrate the HilE, nominally a repressor of SPI-1 gene expression, can also function as an activator under the growth conditions investigated. Collectively, these results provide new insights regarding SPI-1 gene regulation and demonstrate that HilE is more complex than initially envisioned.
Authors: Luary C Martínez; Helen Yakhnin; Martha I Camacho; Dimitris Georgellis; Paul Babitzke; José L Puente; Víctor H Bustamante Journal: Mol Microbiol Date: 2011-05-12 Impact factor: 3.501
Authors: David A Cano; Gustavo Domínguez-Bernal; Alberto Tierrez; Francisco Garcia-Del Portillo; Josep Casadesús Journal: Genetics Date: 2002-12 Impact factor: 4.562