RNAs: regulators of bacterial virulence

Gripenland, Jonas; Netterling, Sakura; Loh, Edmund; Tiensuu, Teresa; Toledo‐Arana, Alejandro; Johansson, Jörgen

doi:10.1038/nrmicro2457

Cited by 174 publications

(167 citation statements)

References 108 publications

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“…1.1): For instance, in bacterial pathogens a wealth of sRNAs have been found to play profound regulatory roles not only in physiology but also pathogenicity (reviewed in Caldelari et al, 2013;Gripenland et al, 2010;Hebrard et al, 2012;Vogel, 2010, 2014;Toledo-Arana et al, 2007). In Salmonella, genome-wide expression analyses under various infection-related conditions have begun to identify potential virulence-related sRNAs.…”

Section: Non-coding Rnas Involved In Virulence Infection and Immunitymentioning

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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Section: Non-coding Rnas Involved In Virulence Infection and Immunitymentioning

confidence: 99%

Dual RNA-seq of pathogen and host

2012

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“…Among these mechanisms, RNA-mediated regulation provides bacteria with an efficient strategy to quickly respond to environmental stimuli [1,2]. Ribonucleases (RNases) play a critical role in RNA metabolism and have been largely associated with the regulation of factors involved in bacterial pathogenicity [3,4].…”

Section: Introductionmentioning

confidence: 99%

RNase Y-mediated regulation of the streptococcal pyrogenic exotoxin B

et al. 2018

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Endoribonuclease Y (RNase Y) is a crucial regulator of virulence in Gram-positive bacteria. In the human pathogen Streptococcus pyogenes, RNase Y is required for the expression of the major secreted virulence factor streptococcal pyrogenic exotoxin B (SpeB), but the mechanism involved in this regulation remains elusive. Here, we demonstrate that the 5′ untranslated region of speB mRNA is processed by several RNases including RNase Y. In particular, we identify two RNase Y cleavage sites located downstream of a guanosine (G) residue. To assess whether this nucleotide is required for RNase Y activity in vivo, we mutated it and demonstrate that the presence of this G residue is essential for the processing of the speB mRNA 5′ UTR by RNase Y. Although RNase Y directly targets and processes speB, we show that RNase Y-mediated regulation of speB expression occurs primarily at the transcriptional level and independently of the processing in the speB mRNA 5′ UTR. To conclude, we demonstrate for the first time that RNase Y processing of an mRNA target requires the presence of a G. We also provide new insights on the speB 5′ UTR and on the role of RNase Y in speB regulation.

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“…In several bacteria, the regulatory activity of trans-encoded sRNAs requires the RNA chaperone Hfq (for review, see Vogel and Luisi 2011). sRNAs regulate a wide variety of processes including secretion, iron homeostasis, carbohydrate and intermediate metabolism, central metabolism, quorum sensing, stress responses, and virulence (for review, see Gripenland et al 2010;Gottesman and Storz 2011).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic profiling of the oyster pathogen Vibrio splendidus opens a window on the evolutionary dynamics of the small RNA repertoire in the Vibrio genus

Toffano‐Nioche

Nguyen

Kuchly

et al. 2012

RNA

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Work in recent years has led to the recognition of the importance of small regulatory RNAs (sRNAs) in bacterial regulation networks. New high-throughput sequencing technologies are paving the way to the exploration of an expanding sRNA world in nonmodel bacteria. In the Vibrio genus, compared to the enterobacteriaceae, still a limited number of sRNAs have been characterized, mostly in Vibrio cholerae, where they have been shown to be important for virulence, as well as in Vibrio harveyi. In addition, genome-wide approaches in V. cholerae have led to the discovery of hundreds of potential new sRNAs. Vibrio splendidus is an oyster pathogen that has been recently associated with massive mortality episodes in the French oyster growing industry. Here, we report the first RNA-seq study in a Vibrio outside of the V. cholerae species. We have uncovered hundreds of candidate regulatory RNAs, be it cis-regulatory elements, antisense RNAs, and trans-encoded sRNAs. Conservation studies showed the majority of them to be specific to V. splendidus. However, several novel sRNAs, previously unidentified, are also present in V. cholerae. Finally, we identified 28 trans sRNAs that are conserved in all the Vibrio genus species for which a complete genome sequence is available, possibly forming a Vibrio ''sRNA core.''

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RNAs: regulators of bacterial virulence

Abstract: El artículo seleccionado no se encuentra disponible por ahora a texto completo por no haber sido facilitado todavía por el investigador a cargo del archivo del mismo.

Cited by 174 publications

References 108 publications

Dual RNA-seq of pathogen and host

Dual RNA-seq of pathogen and host

RNase Y-mediated regulation of the streptococcal pyrogenic exotoxin B

Transcriptomic profiling of the oyster pathogen Vibrio splendidus opens a window on the evolutionary dynamics of the small RNA repertoire in the Vibrio genus

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