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  • Article  (15)
  • Salmonella
  • Health Reference Center Academic (Gale)  (15)
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  • 1
    Language: English
    In: Science (New York, N.Y.), 07 December 2018, Vol.362(6419), pp.1156-1160
    Description: Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.
    Keywords: Drug Resistance, Bacterial ; Host-Pathogen Interactions -- Immunology ; Macrophages -- Immunology ; Salmonella Infections -- Drug Therapy ; Salmonella Typhimurium -- Metabolism ; Type III Secretion Systems -- Metabolism
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 2
    Language: English
    In: PLoS ONE, 2011, Vol.6(3), p.e17296
    Description: P-bodies are dynamic aggregates of RNA and proteins involved in several post-transcriptional regulation processes. P-bodies have been shown to play important roles in regulating viral infection, whereas their interplay with bacterial pathogens, specifically intracellular bacteria that extensively manipulate host cell pathways, remains unknown. Here, we report that Salmonella infection induces P-body disassembly in a cell type-specific manner, and independently of previously characterized pathways such as inhibition of host cell RNA synthesis or microRNA-mediated gene silencing. We show that the Salmonella -induced P-body disassembly depends on the activation of the SPI-2 encoded type 3 secretion system, and that the secreted effector protein SpvB plays a major role in this process. P-body disruption is also induced by the related pathogen, Shigella flexneri , arguing that this might be a new mechanism by which intracellular bacterial pathogens subvert host cell function.
    Keywords: Research Article ; Biology ; Medicine ; Infectious Diseases ; Microbiology ; Molecular Biology ; Cell Biology
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: Nature, 28 January 2016, Vol.529(7587), pp.496-501
    Description: Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.
    Keywords: Gene Expression Regulation -- Genetics ; Host-Pathogen Interactions -- Genetics ; RNA, Bacterial -- Genetics ; RNA, Untranslated -- Genetics ; Salmonella Typhimurium -- Genetics
    ISSN: 00280836
    E-ISSN: 1476-4687
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  • 4
    In: Molecular Microbiology, September 2009, Vol.73(5), pp.737-741
    Description: Small regulatory RNAs (sRNAs) are well known to command bacterial protein synthesis by modulating the translation and decay of target mRNAs. Most sRNAs are specifically regulated by a cognate transcription factor under certain growth or stress conditions. Investigations of the conserved Hfq‐dependent MicM sRNA in (article by Poul Valentin‐Hansen and colleagues in this issue of ) and in have unravelled a novel type of gene regulation in which the chitobiose operon mRNA acts as an RNA trap to degrade the constitutively expressed MicM sRNA, thereby alleviating MicM‐mediated repression of the synthesis of the YbfM porin that is required for chitosugar uptake. The results suggest that ‘target’ mRNAs might be both prey and also predators of sRNAs.
    Keywords: Protein Synthesis ; Messenger Rna;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 5
    In: Molecular Microbiology, January 2009, Vol.71(1), pp.1-11
    Description: species are enterobacterial pathogens that have been exceptionally well investigated with respect to virulence mechanisms, microbial pathogenesis, genome evolution and many fundamental pathways of gene expression and metabolism. While these studies have traditionally focused on protein functions, has also become a model organism for RNA‐mediated regulation. The present review is dedicated to the non‐coding RNA world of : it covers small RNAs (sRNAs) that act as post‐transcriptional regulators of gene expression, novel Salmonella ‐regulatory RNA elements that sense metabolite and metal ion concentrations (or temperature), and globally acting RNA‐binding proteins such as CsrA or Hfq (inactivation of which cause drastic phenotypes and virulence defects). Owing to mosaic genome structure, some of the sRNAs are widely conserved in bacteria whereas others are very specific to species. Intriguingly, sRNAs of either type (CsrB/C, InvR, SgrS) facilitate cross‐talk between the core genome and its laterally acquired virulence regions. Work in also identified physiological functions (and mechanisms thereof) of RNA that had remained unknown in , and pioneered the use of high‐throughput sequencing technology to identify the sRNA and mRNA targets of bacterial RNA‐binding proteins.
    Keywords: Metabolites ; Proteins ; Messenger Rna ; Salmonella ; Gene Expression;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 6
    In: Molecular Microbiology, September 2011, Vol.81(5), pp.1144-1165
    Description: GcvB is one of the most highly conserved Hfq‐associated small RNAs in Gram‐negative bacteria and was previously reported to repress several ABC transporters for amino acids. To determine the full extent of GcvB‐mediated regulation in , we combined a genome‐wide experimental approach with biocomputational target prediction. Comparative pulse expression of wild‐type versus mutant sRNA variants revealed that GcvB governs a large post‐transcriptional regulon, impacting ∼1% of all genes via its conserved G/U‐rich domain R1. Complementary predictions of C/A‐rich binding sites in mRNAs and reporter fusion experiments increased the number of validated GcvB targets to more than 20, and doubled the number of regulated amino acid transporters. Unlike the previously described targeting via the single R1 domain, GcvB represses the glycine transporter CycA by exceptionally redundant base‐pairing. This novel ability of GcvB is focused upon the one target that could feedback‐regulate the glycine‐responsive synthesis of GcvB. Several newly discovered mRNA targets involved in amino acid metabolism, including the global regulator Lrp, question the previous assumption that GcvB simply acts to limit unnecessary amino acid uptake. Rather, GcvB rewires primary transcriptional control circuits and seems to act as a distinct regulatory node in amino acid metabolism.
    Keywords: Glycine -- Physiological Aspects ; Genetic Research -- Physiological Aspects ; Genomics -- Physiological Aspects ; Messenger Rna -- Physiological Aspects;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 7
    In: PLoS Pathogens, 2017, Vol.13(2)
    Description: The transcriptome is a powerful proxy for the physiological state of a cell, healthy or diseased. As a result, transcriptome analysis has become a key tool in understanding the molecular changes that accompany bacterial infections of eukaryotic cells. Until recently, such transcriptomic studies have been technically limited to analyzing mRNA expression changes in either the bacterial pathogen or the infected eukaryotic host cell. However, the increasing sensitivity of high-throughput RNA sequencing now enables “dual RNA-seq” studies, simultaneously capturing all classes of coding and noncoding transcripts in both the pathogen and the host. In the five years since the concept of dual RNA-seq was introduced, the technique has been applied to a range of infection models. This has not only led to a better understanding of the physiological changes in pathogen and host during the course of an infection but has also revealed hidden molecular phenotypes of virulence-associated small noncoding RNAs that were not visible in standard infection assays. Here, we use the knowledge gained from these recent studies to suggest experimental and computational guidelines for the design of future dual RNA-seq studies. We conclude this review by discussing prospective applications of the technique.
    Keywords: Review ; Biology And Life Sciences ; Research And Analysis Methods ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Research And Analysis Methods
    ISSN: 1553-7366
    E-ISSN: 1553-7374
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  • 8
    In: PLoS Genetics, 2016, Vol.12(4)
    Description: While an increasing number of conserved small regulatory RNAs (sRNAs) are known to function in general bacterial physiology, the roles and modes of action of sRNAs from horizontally acquired genomic regions remain little understood. The IsrK sRNA of Gifsy-1 prophage of Salmonella belongs to the latter class. This regulatory RNA exists in two isoforms. The first forms, when a portion of transcripts originating from isrK promoter reads-through the IsrK transcription-terminator producing a translationally inactive mRNA target. Acting in trans , the second isoform, short IsrK RNA, binds the inactive transcript rendering it translationally active. By switching on translation of the first isoform, short IsrK indirectly activates the production of AntQ, an antiterminator protein located upstream of isrK . Expression of antQ globally interferes with transcription termination resulting in bacterial growth arrest and ultimately cell death. Escherichia coli and Salmonella cells expressing AntQ display condensed chromatin morphology and localization of UvrD to the nucleoid. The toxic phenotype of AntQ can be rescued by co-expression of the transcription termination factor, Rho, or RNase H, which protects genomic DNA from breaks by resolving R-loops. We propose that AntQ causes conflicts between transcription and replication machineries and thus promotes DNA damage. The isrK locus represents a unique example of an island-encoded sRNA that exerts a highly complex regulatory mechanism to tune the expression of a toxic protein. Author Summary As the function of conserved core-genome-encoded small RNAs (sRNA) reflects the basic lifestyle of bacteria, the function of non-conserved island-encoded sRNAs remains enigmatic. The island-encoded sRNA IsrK belongs to Gifsy-1 prophage of Salmonella . Here, we report a complex mechanism in which the IsrK RNA functions as both sRNA and mRNA to control the production of the toxic AntQ protein. The isrK promoter directs the synthesis of two distinct RNA species: a full-length translationally inactive target mRNA and the correctly terminated, shorter IsrK sRNA. IsrK sRNA binds the full-length inactive mRNA producing an antiterminator protein, AntQ, which interferes with transcription termination. Expression of antQ results in bacterial growth arrest and ultimately cell death. Fluorescence microscopy of E . coli and Salmonella expressing antQ revealed condensed chromatin morphology as observed upon exposure to DNA-damaging agents. We propose that expression of the phage antiterminator protein results in conflicts between transcription and replication machineries and thus facilitates DNA damage. In summary, the RNA regulator IsrK presents a new regulatory principle in which a horizontally acquired sRNA controls genome integrity.
    Keywords: Research Article ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Research And Analysis Methods ; Biology And Life Sciences ; Biology And Life Sciences ; Research And Analysis Methods ; Research And Analysis Methods ; Biology And Life Sciences
    ISSN: 1553-7390
    E-ISSN: 1553-7404
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  • 9
    Language: English
    In: PLoS Genetics, 01 June 2018, Vol.14(6), p.e1007401
    Description: Invasion of epithelial cells by Salmonella enterica requires expression of genes located in the pathogenicity island I (SPI-1). The expression of SPI-1 genes is very tightly regulated and activated only under specific conditions. Most studies have focused on the regulatory pathways that induce...
    Keywords: Biology
    ISSN: 1553-7390
    E-ISSN: 1553-7404
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  • 10
    In: Molecular Microbiology, October 2009, Vol.74(1), pp.139-158
    Description: The small RNA, ArcZ (previously RyhA/SraH), was discovered in several genome‐wide screens in and . Its high degree of genomic conservation, its frequent recovery by shotgun sequencing, and its association with the RNA chaperone, Hfq, identified ArcZ as an abundant enterobacterial ‘core’ small RNA, yet its function remained unknown. Here, we report that ArcZ acts as a post‐transcriptional regulator in , repressing the mRNAs of the widely distributed (serine uptake) and (oxidative stress) genes, and of STM3216, a horizontally acquired methyl‐accepting chemotaxis protein (MCP). Both and STM3216 are regulated by sequestration of the ribosome binding site. In contrast, the mRNA is targeted in the coding sequence (CDS), arguing that CDS targeting is more common than appreciated. Transcriptomic analysis of an deletion strain further argued for the existence of a distinct set of loci specifically regulated by ArcZ. In contrast, increased expression of the sRNA altered the steady‐state levels of 〉 16% (〉 750) of all mRNAs, and rendered the bacteria non‐motile. Deep sequencing detected a dramatically changed profile of Hfq‐bound sRNAs and mRNAs, suggesting that the unprecedented pleiotropic effects by a single sRNA might in part be caused by altered post‐transcriptional regulation.
    Keywords: Biology;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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