Control of Salmonella pathogenicity island-2 gene expression

Fass, Ephraim; Groisman, Eduardo A.

doi:10.1016/j.mib.2009.01.004

Cited by 190 publications

(186 citation statements)

References 51 publications

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“…Under noninducing conditions, these proteins are likely to be associated with regulatory regions of SPI-2 to silence gene transcription (12,13). When activated within macrophages, the SsrB protein promotes transcription of SPI-2, possibly by counteracting the H-NS-and YdgT-mediated repression (7). Indeed, deletion of the ydgT gene attenuated Salmonella virulence in a mouse infection model, which may have resulted from the expression of SPI-2 genes with inappropriate timing (i.e., under repressing conditions) and/or at inappropriate levels under inducing conditions (12,34).…”

Section: Discussionmentioning

confidence: 99%

Salmonella pathogenicity island 2 expression negatively controlled by EIIA ^Ntr –SsrB interaction is required for Salmonella virulence

Choi

Shin

Yoon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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SsrA/SsrB is a primary two-component system that mediates the survival and replication of Salmonella within host cells. When activated, the SsrB response regulator directly promotes the transcription of multiple genes within Salmonella pathogenicity island 2 (SPI-2). As expression of the SsrB protein is promoted by several transcription factors, including SsrB itself, the expression of SPI-2 genes can increase to undesirable levels under activating conditions. Here, we report that Salmonella can avoid the hyperactivation of SPI-2 genes by using ptsN-encoded EIIA Ntr , a component of the nitrogen-metabolic phosphotransferase system. Under SPI-2-inducing conditions, the levels of SsrB-regulated gene transcription increased abnormally in a ptsN deletion mutant, whereas they decreased in a strain overexpressing EIIA Ntr . We found that EIIA Ntr controls SPI-2 genes by acting on the SsrB protein at the posttranscriptional level. EIIA Ntr interacted directly with SsrB, which prevented the SsrB protein from binding to its target promoter. Finally, the Salmonella strain, either lacking the ptsN gene or overexpressing EIIA Ntr , was unable to replicate within macrophages, and the ptsN deletion mutant was attenuated for virulence in mice. These results indicated that normal SPI-2 gene expression maintained by an EIIA Ntr -SsrB interaction is another determinant of Salmonella virulence.virulence gene regulation | nitrogen-metabolic phosphotransferase system (PTS) | protein-protein interaction

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Section: Discussionmentioning

confidence: 99%

Salmonella pathogenicity island 2 expression negatively controlled by EIIA ^Ntr –SsrB interaction is required for Salmonella virulence

Choi

Shin

Yoon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Nonetheless, its overexpression attenuates the virulence of Salmonella at later time points of the infection (20). In this context, the transcriptional control of SPI2 expression through the RNS-mediated modifications of SsrB Cys 203 , anal- ogous to the importance that YdgT-and Hha-mediated silencing, is important for Salmonella virulence (20,25).…”

Section: Discussionmentioning

confidence: 99%

Redox sensor SsrB Cys ²⁰³ enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection

Husain¹,

Jones-Carson

Song³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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We show herein that the Salmonella pathogenicity island 2 (SPI2) response regulator SsrB undergoes S-nitrosylation upon exposure of Salmonella to acidified nitrite, a signal encountered by this enteropathogen in phagosomes of macrophages. Mutational analysis has identified Cys 203 in the C-terminal dimerization domain of SsrB as the redox-active residue responding to nitric oxide (NO) congeners generated in the acidification of nitrite. Peroxynitrite and products of the autooxidation of NO in the presence of oxygen, but not hydrogen peroxide, inhibit the DNA-binding capacity of SsrB, demonstrating the selectivity of the reaction of Cys 203 with reactive nitrogen species (RNS). These findings identify the twocomponent response regulator SsrB Cys 203 as a thiol-based redox sensor. A C203S substitution protects SsrB against the attack of RNS while preserving its DNA-binding capacity. When exposed to SPI2-inducing conditions, Salmonella expressing the wild-type ssrB allele or the ssrB C203S variant sustain transcription of the sifA, sspH2, and srfJ effector genes. Nonetheless, compared with the strain expressing a redox-resistant SsrB C203S variant, wild-type Salmonella bearing the NO-responsive allele exhibit increased fitness when exposed to RNS in an NRAMP R , C3H/HeN murine model of acute oral infection. Given the widespread occurrence of the wildtype allele in Salmonella enterica, these findings indicate that SsrB Cys 203 increases Salmonella virulence by serving as a redox sensor of NO resulting from the host immune response to oral infection.macrophages | pathogenesis | two-component regulatory system

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“…Upon its stimulation, HilD transcriptionally activates two further regulators, HilC and RtsA, which amplify the signal, leading to the rapid induction of the entire SPI-1 locus. Choi and Groisman, 2013, Ellermeier and Slauch, 2007, and Fass and Groisman, 2009 In contrast, the T3SS-2 routes effectors across the vacuolar membrane of Salmonella's intracellular replication niche, the so-called Salmonella-containing vacuole (SCV). Thus, expression of SPI-2 has to be tightly controlled to ensure its activation only within the host cell environment.…”

Section: Salmonella As a Model Organism For Host-pathogen Interactionmentioning

confidence: 99%

“…Thus, expression of SPI-2 has to be tightly controlled to ensure its activation only within the host cell environment. This precision is mediated by various upstream positive and negative regulators, including the two-component systems OmpR/EnvZ and PhoQ/PhoP, that sense environmental factors and feed into the regulatory network (Fass and Groisman, 2009) (Fig. 1.2).…”

Section: Salmonella As a Model Organism For Host-pathogen Interactionmentioning

confidence: 99%

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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Control of Salmonella pathogenicity island-2 gene expression

Cited by 190 publications

References 51 publications

Salmonella pathogenicity island 2 expression negatively controlled by EIIA ^Ntr –SsrB interaction is required for Salmonella virulence

Salmonella pathogenicity island 2 expression negatively controlled by EIIA ^Ntr –SsrB interaction is required for Salmonella virulence

Redox sensor SsrB Cys ²⁰³ enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection

Dual RNA-seq of pathogen and host

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Control of Salmonella pathogenicity island-2 gene expression

Cited by 190 publications

References 51 publications

Salmonella pathogenicity island 2 expression negatively controlled by EIIA Ntr –SsrB interaction is required for Salmonella virulence

Salmonella pathogenicity island 2 expression negatively controlled by EIIA Ntr –SsrB interaction is required for Salmonella virulence

Redox sensor SsrB Cys 203 enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection

Dual RNA-seq of pathogen and host

Contact Info

Product

Resources

About

Salmonella pathogenicity island 2 expression negatively controlled by EIIA ^Ntr –SsrB interaction is required for Salmonella virulence

Salmonella pathogenicity island 2 expression negatively controlled by EIIA ^Ntr –SsrB interaction is required for Salmonella virulence

Redox sensor SsrB Cys ²⁰³ enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection