Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The small RNA Teg41 Regulates Expression of the alpha Phenol Soluble Modulins and is Required for Virulence in Staphylococcus aureus

ABSTRACT: Small RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria. Hundreds of sRNAs have been identified in the major human pathogen Staphylococcus aureus; however, only a few have been characterized in detail. In this study we investigate the role of the sRNA Teg41 in S. aureus virulence. We demonstrate that Teg41, an sRNA divergently transcribed from the locus that encodes the cytolytic alpha phenol soluble modulin (αPSM) peptides, plays a critical role in αPSM production. Overproduction of Teg41 leads to an increase in αPSM levels and a corresponding increase in hemolytic activity from S. aureus cells and cell-free culture supernatants. We demonstrate that the increase in αPSM production is post-transcriptional, as expression of the αPSM transcript is unaltered upon Teg41 overproduction. To identify regions of Teg41 important for its function we performed an in silico RNA:RNA interaction analysis which predicted an interaction between the 3’ end of Teg41 and the αPSM transcript. Deleting a 24-nucleotide region from the S. aureus genome, corresponding to the 3’ end of Teg41, led to a 10-fold reduction in αPSM-dependent hemolytic activity and attenuation of virulence in a murine abscess model of infection. Together these results demonstrate, for the first time, post-transcriptional regulation of the αPSM peptides by an sRNA in S. aureus.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE108336 | GEO | 2019/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The Small RNA Teg41 Is a Pleiotropic Regulator of Virulence in Staphylococcus aureus [wt teg41]

Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.

2022-09-29 | GSE203564 | GEO

The Small RNA Teg41 Is a Pleiotropic Regulator of Virulence in Staphylococcus aureus [teg41 psm]

2022-09-29 | GSE203563 | GEO

The small RNA Teg41 is a pleiotropic regulator of virulence and stress response in Staphylococcus aureus

Project description:In this study, we further characterize the regulation of the αPSM transcript by Teg41. We show that a single chromosomally integrated copy of Teg41 restores virulence, hemolysis, extracellular vesicle production, and αPSM production in a strain deleted for the 3’ end of Teg41 (Teg41Δ3′ strain). We show that substituting four Teg41 nucleotides in the predicted Teg41- αPSM interaction site abolishes increased hemolysis in a Teg41 overexpression strain. We go on to demonstrte that Teg41 expression influences both the stability and abundance of the αPSM transcript, and, interestingly, that the Teg41Δ3′ strain shows decreased stability in more than 50 transcripts and altered expression levels in over 900 transcripts when compared to wild type S. aureus. Finally, we observe that Teg41 plays a role in S. aureus stress response and that the Teg41Δ3′ strain is more severely attenuated in murine systemic infection than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.

2021-10-07 | GSE185262 | GEO

The small RNA SprY controls RNAIII function and affects Staphylococcus aureus virulence

Project description:While a plethora of small regulatory RNAs (sRNAs) have been identified in the human pathogen Staphylococcus aureus, the physiological function of most of them remains unknown. We report the characterization of SprY, a sRNA from S. aureus expressed from a pathogenicity island. RNAIII, a major regulator of S. aureus virulence, was discovered as a potential SprY target by an MS2-affinity purification assay. In silico interaction studies suggest a RNA-RNA pairing between the SprY 5’end and the 13rd stem-loop of RNAIII. Overproduction of SprY leads to a 1.5-fold reduction of RNAIII amount. By affecting the rnaIII expression, SprY affects the amount of RNAIII known targets. Indeed, SprY downregulates hla mRNA translation, but also upregulates other secreted factors such as Ecb and Rot. Furthermore, SprY decreases the hemolytic activity and virulence of S. aureus. Our results lead to propose that SprY is involved in S. aureus virulence through a post-transcriptional regulation of RNAIII.

2021-02-10 | GSE166499 | GEO

The small RNA Teg41 is a pleiotropic regulator of virulence in Staphylococcus aureus

2022-10-03 | PXD034014 | Pride

RNase III CLASH uncovers sRNA regulatory networks coupling metabolism to production of cytolytic toxins in methicillin resistant Staphylococcus aureus

Project description:Methicillin resistant Staphylococcus aureus (MRSA) is an infectious pathogen that poses a significant threat to human health. MRSA is renowned for its ability to adapt to and even thrive in hostile environment within its host. By expressing a battery of virulence factors and toxins, MRSA is able to scavenge effectively essential nutrients and evade the immune system within the host. Post-transcriptional regulation by sRNAs contributes significantly to regulating the expression of virulence factors and toxins. However, the roles of the vast majority of sRNAs during host adaptation remain unknown. To challenge this gap, we performed UV cross-linking, ligation and sequencing of hybrids (CLASH) in S. aureus to unravel sRNA-RNA interactions with the double stranded ribonuclease III (RNase III) as a bait under conditions that mimic the host environment. Here we report a global analysis of RNA-RNA interactions in MRSA in vivo, which uncovered hundreds of novel sRNA-RNA pairs. Strikingly, our results indicate that the production of small membrane-permeabilizing toxins is under extensive sRNA-mediated regulation and that their expression is intimately connected to metabolism. We show that at least two sRNAs, RNAIII and RsaE, enhance the production of five clinically relevant cytolytic toxins that are important for survival within the host. Taken together, our data greatly expands the repertoire of sRNA-target interactions in S. aureus and provide detail on how these contribute to adjusting virulence in response to changes in metabolism.

2022-06-16 | PXD025122 | Pride

RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression

Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen responsible for high levels of human morbidity and mortality. MRSA co-ordinates expression of an array of bacterial factors involved in antimicrobial resistance, nutrient acquisition and immune evasion in the host. Post-transcriptional regulation by small RNAs (sRNAs) has emerged as an important mechanism for the control of MRSA virulence. However, the function of the majority of sRNAs during infection is unknown. To address this gap in understanding, we performed UV cross-linking, ligation and sequencing of hybrids (CLASH) in MRSA to unravel sRNA-RNA interactions under conditions that mimic the host environment. Using double stranded ribonuclease III (RNase III) as a bait we not only uncovered known interactions but also hundreds of novel sRNA-RNA pairs. Strikingly, our results suggest that the production of small membrane-permeabilizing toxins is under extensive sRNA-mediated regulation and that their expression is intimately connected to metabolism. Importantly, we discovered that two sRNAs, RNAIII and RsaE, control the expression of at least four cytolytic toxins that are important for MRSA virulence. Taken together, we present a comprehensive analysis of sRNA-target interactions in S. aureus and provide detail on how these contribute to the control of virulence in response to changes in metabolism.

2022-05-04 | GSE166151 | GEO

Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus

Project description:In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome anno- tation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. Four RNAseq data sets in total. Each sample was generated by pooling three independent biological replicate RNA preps

2016-01-05 | E-GEOD-74936 | biostudies-arrayexpress

Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus

2016-01-05 | GSE74936 | GEO

The effect of RsaI on global gene expression in S. aureus

Project description:The virulon of Staphyloccocus aureus is controlled by intricate connections between transcriptional and post-transcriptional regulators including proteins and small non coding RNAs (sRNAs). Most of the sRNAs regulate gene expression through base-pairings with mRNAs. Here, we have determined the transcriptome of RsaI sRNA of S. aureus.

2018-11-02 | GSE122064 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data