The Salmonella selC locus contains a pathogenicity island mediating intramacrophage survival

Blanc‐Potard, Anne‐Béatrice; Groisman, Eduardo A.

doi:10.1093/emboj/16.17.5376

Cited by 321 publications

(345 citation statements)

References 45 publications

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“…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. In summary, characteristic expression signatures of virulence genes fit the dogma of SPI-1 genes being required for host cell invasion and SPI-2 genes for intracellular survival and replication, thereby providing proof-of-principle for Dual RNA-seq to reliably capture Salmonella's intracellular gene expression changes.…”

Section: Figure 219|salmonella Virulence Gene Expression Patterns Insupporting

confidence: 66%

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: 66%

Dual RNA-seq of pathogen and host

2012

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“…Y. pestis produced fluorescence levels similar to those of S. enterica when transcription of a promoterless gfp gene was driven by the promoter of the mgtA gene (Fig. 1B), which is found in most enteric species (24). By contrast, Yersinia elicited significantly lower fluorescence than Salmonella when gfp was expressed from the promoter of the Salmonellaspecific ugtL gene (Fig.…”

Section: Differential Ability Of the Yersinia Phop Protein To Expressmentioning

confidence: 72%

“…Given the degree of sequence identity between the sensing domains of the Salmonella and Yersinia PhoQ proteins (35), the virulence attenuation of the Salmonella strain expressing the Yersinia phoPQ operon is unlikely to result from a defect in the sensing ability of the Yersinia PhoQ protein. Rather, it may ref lect that Salmonella virulence demands the expression of horizontally acquired PhoP-dependent genes, such as mig-14 (36) and mgtC (24), whose promoters share the location and orientation of the PhoP box with the ugtL promoter (Fig. 3A) and thus are not efficiently transcribed by the Y. pestis PhoP protein (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…3 B and C). Thus, we wondered whether the Salmonella PhoP protein could promote transcription from the Yersinia mgtC promoter (the Salmonella and Yersinia mgtC genes are xenologs rather than orthologs, because they seem to have been acquired independently by the Salmonella and Yersinia lineages) (24,27). The Salmonella PhoP protein could not promote transcription of the Yersinia mgtC gene (Fig.…”

Section: Promoter Architecture Dictates the Ability Of The Salmonellamentioning

confidence: 99%

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Transcription factor function and promoter architecture govern the evolution of bacterial regulons

Pérez

Groisman

2009

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

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Evolutionary changes in ancestral regulatory circuits can bring about phenotypic differences between related organisms. Studies of regulatory circuits in eukaryotes suggest that these modifications result primarily from changes in cis-regulatory elements (as opposed to alterations in the transcription factors that act upon these sequences). It is presently unclear how the evolution of gene regulatory circuits has proceeded in bacteria, given the rampant effects of horizontal gene transfer, which has significantly altered the composition of bacterial regulons. We now demonstrate that the evolution of the regulons governed by the regulatory protein PhoP in the related human pathogens Salmonella enterica and Yersinia pestis has entailed functional changes in the PhoP protein as well as in the architecture of PhoP-dependent promoters. These changes have resulted in orthologous PhoP proteins that differ both in their ability to promote transcription and in their role as virulence regulators. We posit that these changes allow bacterial transcription factors to incorporate newly acquired genes into ancestral regulatory circuits and yet retain control of the core members of a regulon.cis-regulatory elements ͉ horizontal gene transfer ͉ PhoP ͉ Salmonella ͉ Yersinia

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“…MgtCp has been shown to be a virulence factor important for the proliferation of several intracellular bacterial pathogens in macrophages (1,4,27). The function of MgtCp is unknown, but it seems to facilitate or regulate Mg 2ϩ transport since it is required for growth at low Mg 2ϩ concentrations (11).…”

mentioning

confidence: 99%