Two promoters and two translation start sites control the expression of the Shigella flexneri outer membrane protease IcsP

Hensley, Christopher T.; Kamneva, Olga K.; Levy, Karen M.; Labahn, Stephanie K.; Africa, Lia A.; Wing, Helen J.

doi:10.1007/s00203-010-0669-2

Cited by 14 publications

(24 citation statements)

References 35 publications

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“…Promoter activity of this gene was measured using a plasmid-borne P icsP-lacZ reporter in both E. coli and Shigella backgrounds [50,52]. While 5′ truncation analyses of the icsP promoter reveal that the DNA sequences located between 800 and 350 bp upstream of the primary icsP TSS are required for H-NS-mediated repression [60], the VirB binding site required for transcriptional anti-silencing of this promoter lies over 1 kb upstream of the primary icsP TSS [52,61]. To date, it remains unclear how silencing and anti-silencing of the icsP promoter occurs from such remote sites.…”

Section: H-ns and Its Role In The Regulatory Cascade Controlling Tmentioning

confidence: 99%

H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species

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Wing

2016

Genes

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The histone-like nucleoid structuring protein (H-NS) has played a key role in shaping the evolution of Shigella spp., and provides the backdrop to the regulatory cascade that controls virulence by silencing many genes found on the large virulence plasmid. H-NS and its paralogue StpA are present in all four Shigella spp., but a second H-NS paralogue, Sfh, is found in the Shigella flexneri type strain 2457T, which is routinely used in studies of Shigella pathogenesis. While StpA and Sfh have been proposed to serve as “molecular backups” for H-NS, the apparent redundancy of these proteins is questioned by in vitro studies and work done in Escherichia coli. In this review, we describe the current understanding of the regulatory activities of the H-NS family members, the challenges associated with studying these proteins and their role in the regulation of virulence genes in Shigella.

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Section: H-ns and Its Role In The Regulatory Cascade Controlling Tmentioning

confidence: 99%

H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species

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Wing

2016

Genes

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“…In contrast to icsA expression, which is primarily regulated by the transcriptional activator VirF (1,21,36), our previous studies have revealed that expression of icsP is regulated by VirB (4,18,46), a transcriptional activator whose expression is controlled directly by VirF. VirB, which directly controls the expression of many virulence-associated genes carried on the Shigella virulence plasmid (4,21,46), is maximally produced at 37°C, the temperature within the human host (30).…”

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confidence: 94%

The Iron-Responsive Fur/RyhB Regulatory Cascade Modulates the Shigella Outer Membrane Protease IcsP

et al. 2011

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Actin-based motility is central to the pathogenicity of the intracellular bacterial pathogen Shigella. Two Shigella outer membrane proteins, IcsA and IcsP, are required for efficient actin-based motility in the host cell cytoplasm, and the genes encoding both proteins are carried on the large virulence plasmid. IcsA triggers actin polymerization on the surface of the bacterium, leading to the formation of an actin tail that allows both intraand intercellular spread. IcsP, an outer membrane protease, modulates the amount and distribution of the IcsA protein on the bacterial surface through proteolytic cleavage of IcsA. Transcription of icsP is increased in the presence of VirB, a DNA-binding protein that positively regulates many genes carried on the large virulence plasmid. In Shigella dysenteriae, the small regulatory RNA RyhB, which is a member of the iron-responsive Fur regulon, suppresses several virulence-associated phenotypes by downregulating levels of virB in response to iron limitation. Here we show that the Fur/RyhB regulatory pathway downregulates IcsP levels in response to low iron concentrations in Shigella flexneri and that this occurs at the level of transcription through the RyhB-dependent regulation of VirB. These observations demonstrate that in Shigella species the Fur/RyhB regulatory pathway provides a mechanism to finely tune the expression of icsP in response to the low concentrations of free iron predicted to be encountered within colonic epithelial cells.

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“…2A) (14). Although it is possible that the LacZ protein is more stably maintained in the S. flexneri background than in E. coli, leading to higher ␤-galactosidase activity, this seems unlikely because LacZ activity has been shown to decline during stationary phase, when lacZ is expressed from another promoter in S. flexneri (39).…”

Section: Resultsmentioning

confidence: 99%

Characterization of SlyA in Shigella flexneri Identifies a Novel Role in Virulence

Weatherspoon-Griffin

Wing

2016

Infect Immun

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The SlyA transcriptional regulator has important roles in the virulence and pathogenesis of several members of the Enterobacteriaceae family, including Salmonella enterica serovar Typhimurium and Escherichia coli. Despite the identification of the slyA gene in Shigella flexneri nearly 2 decades ago, as well as the significant conservation of SlyA among enteric bacteria, the role of SlyA in Shigella remains unknown. The genes regulated by SlyA in closely related organisms often are absent from or mutated in S. flexneri, and consequently many described SlyA-dependent phenotypes are not present. By characterizing the expression of slyA and determining its ultimate effect in this highly virulent organism, we postulated that novel SlyA-regulated virulence phenotypes would be identified. In this study, we report the first analysis of SlyA in Shigella and show that (i) the slyA gene is transcribed and ultimately translated into protein, (ii) slyA promoter activity is maximal during stationary phase and is negatively autoregulated and positively regulated by the PhoP response regulator, (iii) the exogenous expression of slyA rescues transcription and virulence-associated deficiencies during virulence-repressed conditions, and (iv) the absence of slyA significantly decreases acid resistance, demonstrating a novel and important role in Shigella virulence. Cumulatively, our study illustrates unexpected parallels between the less conserved S. flexneri and S. Typhimurium slyA promoters as well as a unique role for SlyA in Shigella virulence that has not been described previously in any closely related organism. The MarR/SlyA family of transcription factors controls an array of biological functions critical to bacterial physiology and survival (1-5). In the Enterobacteriaceae family, the DNA binding protein SlyA regulates diverse aspects of virulence (reviewed in reference 6). SlyA originally was identified in Salmonella enterica serovar Typhimurium for its ability to induce hemolytic and cytotoxic phenotypes when overexpressed in Escherichia coli (7,8). Since then, in S. Typhimurium, SlyA has been implicated in facilitating intracellular survival within professional macrophages (7, 9), contributing to cell envelope modification (10), and conferring resistance to antimicrobial peptides and oxidative stress (11,12). Meanwhile, in E. coli, SlyA contributes to virulence differently by inducing a hemolytic phenotype (13), facilitating the synthesis of a virulence antigen (14,15), and contributing to type 1 fimbriation (16). The role of SlyA in the human pathogen Shigella, however, has not been described despite the identification of a slyA gene (8) and the high amino acid identity that SlyA shares with SlyA proteins found in closely related organisms (Table 1).Shigella flexneri is closely related to both Salmonella spp. and E. coli. It carries a large (ϳ220-kb) virulence plasmid responsible for the invasive and virulent nature of this organism. Encoded on the large virulence plasmid is VirB, a transcriptional regulator essential ...

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Two promoters and two translation start sites control the expression of the Shigella flexneri outer membrane protease IcsP

Cited by 14 publications

References 35 publications

H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species

H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species

The Iron-Responsive Fur/RyhB Regulatory Cascade Modulates the Shigella Outer Membrane Protease IcsP

Characterization of SlyA in Shigella flexneri Identifies a Novel Role in Virulence

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