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Regulatory RNAs in Virulence and Host-Microbe Interactions

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  • Author: Alexander J. Westermann1
  • Editors: Gisela Storz3, Kai Papenfort4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Institute of Molecular Infection Biology, University of Würzburg; 2: Helmholtz Institute for RNA-Based Infection Research, D-97080 Würzburg, Germany; 3: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 4: Department of Biology I, Microbiology, LMU Munich, Martinsried, Germany
  • Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0002-2017
  • Received 13 October 2017 Accepted 13 March 2018 Published 13 July 2018
  • Alexander J. Westermann, [email protected]
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  • Abstract:

    Bacterial regulatory RNAs are key players in adaptation to changing environmental conditions and response to diverse cellular stresses. However, while regulatory RNAs of bacterial pathogens have been intensely studied under defined conditions , characterization of their role during the infection of eukaryotic host organisms is lagging behind. This review summarizes our current understanding of the contribution of the different classes of regulatory RNAs and RNA-binding proteins to bacterial virulence and illustrates their role in infection by reviewing the mechanisms of some prominent representatives of each class. Emerging technologies are described that bear great potential for global, unbiased studies of virulence-related RNAs in bacterial model and nonmodel pathogens in the future. The review concludes by deducing common principles of RNA-mediated gene expression control of virulence programs in different pathogens, and by defining important open questions for upcoming research in the field.

  • Citation: Westermann A. 2018. Regulatory RNAs in Virulence and Host-Microbe Interactions. Microbiol Spectrum 6(4):RWR-0002-2017. doi:10.1128/microbiolspec.RWR-0002-2017.

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/content/journal/microbiolspec/10.1128/microbiolspec.RWR-0002-2017
2018-07-13
2018-08-19

Abstract:

Bacterial regulatory RNAs are key players in adaptation to changing environmental conditions and response to diverse cellular stresses. However, while regulatory RNAs of bacterial pathogens have been intensely studied under defined conditions , characterization of their role during the infection of eukaryotic host organisms is lagging behind. This review summarizes our current understanding of the contribution of the different classes of regulatory RNAs and RNA-binding proteins to bacterial virulence and illustrates their role in infection by reviewing the mechanisms of some prominent representatives of each class. Emerging technologies are described that bear great potential for global, unbiased studies of virulence-related RNAs in bacterial model and nonmodel pathogens in the future. The review concludes by deducing common principles of RNA-mediated gene expression control of virulence programs in different pathogens, and by defining important open questions for upcoming research in the field.

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FIGURE 1

Selection of virulence-associated regulatory RNA elements in human pathogens. Representatives of distinct classes of regulatory RNA are indicated (see color code on top). Illustrated are all RNAs referred to in the main text and in Table 1 ; absence of RNAs (e.g., CsrB/C) in a given pathogen does not necessarily imply that they are not encoded by that bacterium, but rather that they are not explicitly mentioned in the text. Several bacterial pathogens may colonize multiple niches and cause more than a single disease in their human host, but they are assigned to just one organ and illness here for the sake of simplicity. GAS, group A .

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0002-2017
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FIGURE 2

Global RBPs contribute to virulence. (a) Virulence phenotypes associated with the deletion of the five major RBPs in Typhimurium: the RNA chaperones Hfq ( 147 , 330 ) and ProQ ( 158 ; Westermann et al., unpublished), the translational regulator CsrA ( 137 ), and the cold shock proteins CspC and CspE ( 162 ). The asterisk (*) indicates that the biofilm formation phenotype of Δ mutants stems from work with ( 161 ). (b) The interactome of the same RBPs in Typhimurium is enriched for virulence-associated mRNAs. Gene ontology enrichment analysis ( 331 , 332 ) on CLIP-seq data for Hfq and CsrA ( 136 ) and RIP-seq data for ProQ ( 158 ) and CspC and CspE ( 162 ). Fold enrichments of all significantly enriched ( < 0.05) pathways are plotted. Virulence-related pathways are in bold.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0002-2017
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FIGURE 3

General lack of phenotypes of virulence-associated RNAs. An Rfam search ( 333 ) for the query term “virulence” yielded 373 hits (as of February 2017). From these, nonbacterial RNAs and CRISPR RNAs were removed. For the remaining 308 entries, a manual literature search revealed whether or not the respective deletion/disruption mutants exhibit a virulence defect in cell culture ( phenotype), live-animal models (), or both.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0002-2017
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FIGURE 4

Common principles of sRNA-based virulence control. (a) The tight interconnection between metabolism and virulence is illustrated by the transcription of certain sRNAs in response to metabolic or infection-related cues, which in turn control virulence regulators/effectors, nutrient transporters, and/or metabolic enzymes. (b) Control of major lifestyle transitions. Upon sensing of a specific trigger, a bacterial sRNA may act in concert with transcription factors (not shown) to coordinate the rapid silencing of genes and degradation of mRNAs no longer needed under the new condition (circuit 1). This mechanism differs from feedback control, where sRNA and target are coactivated by the same stimulus (circuit 2). (c) sRNAs target mRNAs for key regulatory proteins, thereby indirectly controlling the expression of genes that are under the transcriptional control of those regulators. Often this RNA-based regulatory network ensures mutually exclusive activation of opposing processes (exemplified here by motility and virulence effector secretion). (d) Functional redundancy between sRNA homologs. sRNA pairs might arise from gene duplication events and thus share sequence homology, allowing the regulation of shared targets. However, functional redundancy might only be partial, when sibling sRNAs are produced under different conditions, interact with distinct cellular protein partners, or base-pair uniquely with specific mRNAs.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0002-2017
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Tables

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TABLE 1

Virulence-associated regulatory RNA elements in diverse human pathogens

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0002-2017

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