<i>Salmonella</i>
            Pathogenicity Island 4-Mediated Adhesion Is Coregulated with Invasion Genes in
            <i>Salmonella enterica</i>

Gerlach, Roman G.; Jäckel, Daniela; Geymeier, Nina; Hensel, Michael

doi:10.1128/iai.00228-07

Cited by 76 publications

(79 citation statements)

References 36 publications

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“…genes from both islands were intracellularly induced. In agreement with previous findings that reported a co-regulation of SPI-4 with invasion genes (Gerlach et al, 2007), SPI-4 expression was rapidly shut off after invasion, thereby resembling the expression kinetics of SPI-1 factors. Genes from SPI-3 displayed a bipartite expression pattern: The mgt operon was strongly activated inside both cell types according to previous reports (BlancPotard and Groisman, 1997;Hautefort et al, 2008), whereas other SPI-3 genes were repressed.…”

Section: Figure 219|salmonella Virulence Gene Expression Patterns Insupporting

confidence: 92%

Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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Section: Figure 219|salmonella Virulence Gene Expression Patterns Insupporting

confidence: 92%

Dual RNA-seq of pathogen and host

2012

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“…The results of the nonquantitative RT-PCRs are described in Table 3. All the coding and intergenic regions are transcribed, suggesting that siiABCDEF is a single operon, consistent with observations by Gerlach et al (34). Rapid amplification of the 5Ј cDNA ends was employed to map the transcriptional start site of siiA.…”

Section: Resultssupporting

confidence: 64%

“…Regulation of SPI4 has been recently demonstrated to overlap with that of SPI1 (34). Mutations in hilA and sirA cause a significant reduction in SiiE production and SPI4-mediated adherence to epithelial cells (34).…”

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confidence: 99%

“…Mutations in hilA and sirA cause a significant reduction in SiiE production and SPI4-mediated adherence to epithelial cells (34). SPI1 expression is known to respond to a complex cascade of transcriptional regulators and a variety of environmental parameters relevant to the intestine, including osmolarity, oxygen tension, pH, presence of bile, Mg 2ϩ concentration, and presence of short-chain fatty acids (4).…”

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confidence: 99%

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Coordinate Regulation of Salmonella Pathogenicity Island 1 (SPI1) and SPI4 in Salmonella enterica Serovar Typhimurium

et al. 2008

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Salmonella enterica serovar Typhimurium harbors five pathogenicity islands (SPI) required for infection in vertebrate hosts. Although the role of SPI1 in promoting epithelial invasion and proinflammatory cell death has been amply documented, SPI4 has only more recently been implicated in Salmonella virulence. SPI4 is a 24-kb pathogenicity island containing six open reading frames, siiA to siiF. Secretion of the 595-kDa SiiE protein requires a type I secretory system encoded by siiC, siiD, and siiF. An operon polarity suppressor (ops) sequence within the 5 untranslated region upstream of siiA is required for optimal SPI4 expression and predicted to bind the antiterminator RfaH. SiiE concentrations are decreased in a SPI1 mutant strain, suggesting that SPI1 and SPI4 may have common regulatory inputs. SPI1 gene expression is positively regulated by the transcriptional activators HilA, HilC, and HilD, encoded within SPI1, and negatively regulated by the regulators HilE and PhoP. Here, we show that mutations in hilA, hilC, or hilD similarly reduce expression of siiE, and mutations in hilE or phoP enhance siiE expression. Individual overexpression of HilA, HilC, or HilD in the absence of SPI1 cannot activate siiE expression, suggesting that these transcriptional regulators act in concert or in combination with additional SPI1-encoded regulatory loci to activate SPI4. HilA is no longer required for siiE expression in an hns mutant strain, suggesting that HilA promotes SPI4 expression by antagonizing the global transcriptional silencer H-NS. Coordinate regulation suggests that SPI1 and SPI4 play complementary roles in the interaction of S. enterica serovar Typhimurium with the host intestinal mucosa.

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“…Activation of the SPI1 rtsA gene only requires the AraC family activators HilC and HilD if both H-NS and Hha are present [64,65]. The SPI1-encoded transcriptional activator HilA not only promotes expression of SPI1 genes but also appears to counter H-NS silencing of the SPI4 pathogenicity island [66], which acts in concert with SPI1 during Salmonella interactions with the host intestinal mucosa [67]. A requirement for the transcriptional activator SsrB for SPI2 expression is reduced in the absence of H-NS, suggesting that SsrB both activates transcription and relieves H-NS-mediated repression [68].…”

Section: Counter-silencing Of H-ns and Its Functional Consequencesmentioning

confidence: 99%

New insights into transcriptional regulation by H-NS

Fang

Rimsky

2008

Current Opinion in Microbiology

183

173

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H-NS, a nucleoid-associated DNA-binding protein of enteric bacteria, was discovered thirty-five years ago and subsequently found to exert widespread and highly pleiotropic effects on gene regulation. H-NS binds to high-affinity sites and spreads along adjacent AT-rich DNA to silence transcription. Preferential binding to sequences with higher AT-content than the resident genome allows H-NS to repress the expression of foreign DNA in a process known as "xenogeneic silencing." Counter-silencing by a variety of mechanisms facilitates the evolutionary acquisition of horizontally transferred genes and their integration into pre-existing regulatory networks. This review will highlight recent insights into the mechanism and biological importance of H-NS-DNA interactions. H-NS--A Nucleoid ProteinH-NS is an abundant DNA-binding protein implicated in the organization of the bacterial chromosome [1]. H-NS and other nucleoid-associated proteins can affect DNA topology at specific loci, thereby modulating gene transcription. Binding by these proteins is proposed to selectively direct supercoiling effects to promoters [2•]. Mutation of hns alters the responsiveness of transcription to changes in DNA superhelicity. Regulatory effects of supercoiling are linked to metabolic and environmental conditions. Thus, H-NS has been viewed as a nucleoid structuring protein with global effects on gene expression [3].H-NS exists primarily as a dimer at low concentrations but can multimerize into higher order complexes [4,5] that form bridges between adjacent DNA helices [6]. Optical tweezers have been used to demonstrate that H-NS dimers or multimers can simultaneously interact with separate DNA binding sites [7••]. H-NS-coated DNA is not self-interactive, suggesting that dimerization or oligomerization must precede DNA binding for bridging to occur. Force measurements suggest that transcription barriers created by H-NS binding are weak (∼7 pN) and readily overcome, so that H-NS oligomers pose only a relative barrier to translocating RNA polymerase. DNA bridging is a conserved feature of H-NS homologs found in most gram-negative bacteria [8] that appears to constrain large DNA loops [9••] and helps to account for the effects of H-NS on transcription. However, it must be noted that the relationship between bridging as a general effect and the silencing of specific promoters is not yet clear.H-NS is more appropriately viewed as a determinant of chromosomal architecture rather than as a general structural component. The analysis of nucleoids treated with urea suggests that *Corresponding Author : Tel 206-275-0966, Fax 206-616-1575, e-mail : fcfang@u.washington.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production proce...

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Salmonella Pathogenicity Island 4-Mediated Adhesion Is Coregulated with Invasion Genes in Salmonella enterica

Cited by 76 publications

References 36 publications

Dual RNA-seq of pathogen and host

Dual RNA-seq of pathogen and host

Coordinate Regulation of Salmonella Pathogenicity Island 1 (SPI1) and SPI4 in Salmonella enterica Serovar Typhimurium

New insights into transcriptional regulation by H-NS

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