Control of competence by related non-coding csRNAs in Streptococcus pneumoniae R6

Laux, Anke; Sexauer, Anne; Sivaselvarajah, Dineshan; Kaysen, Anne; Brückner, Reinhold

doi:10.3389/fgene.2015.00246

Cited by 29 publications

(30 citation statements)

References 48 publications

(91 reference statements)

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“…The csRNAs are post‐transcriptional repressors of comC mRNA encoding the precursor protein of the pneumococcal competence‐stimulating peptide (CSP). Without synthesis of CSP, competence and therefore DNA uptake from the environment cannot be induced (Schnorpfeil et al , ; Laux et al , ). Molecular details of csRNA‐mediated control and the involvement of RBPs are yet to be determined.…”

Section: Resultsmentioning

confidence: 99%

Grad‐seq in a Gram‐positive bacterium reveals exonucleolytic sRNA activation in competence control

et al. 2020

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RNA-protein interactions are the crucial basis for many steps of bacterial gene expression, including post-transcriptional control by small regulatory RNAs (sRNAs). In stark contrast to recent progress in the analysis of Gram-negative bacteria, knowledge about RNAprotein complexes in Gram-positive species remains scarce. Here, we used the Grad-seq approach to draft a comprehensive landscape of such complexes in Streptococcus pneumoniae, in total determining the sedimentation profiles of~88% of the transcripts and~62% of the proteins of this important human pathogen. Analysis of in-gradient distributions and subsequent tag-based protein capture identified interactions of the exoribonuclease Cbf1/YhaM with sRNAs that control bacterial competence for DNA uptake. Unexpectedly, the nucleolytic activity of Cbf1 stabilizes these sRNAs, thereby promoting their function as repressors of competence. Overall, these results provide the first RNA/protein complexome resource of a Gram-positive species and illustrate how this can be utilized to identify new molecular factors with functions in RNA-based regulation of virulence-relevant pathways.

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Section: Resultsmentioning

confidence: 99%

Grad‐seq in a Gram‐positive bacterium reveals exonucleolytic sRNA activation in competence control

et al. 2020

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“…While this explains the need for upregulation of rpoD, the underlying mechanism is still unknown. Other aspects that might play a role in the shutting down of competence are the CiaR-mediated upregulation of HtrA, which has been shown to degrade extracellular CSP (9), and the recently discovered CiaR-regulated non-coding csRNAs (ccnA-E) (30,90,91), which were shown to repress ComC translation in an additive fashion.…”

Section: Discussionmentioning

confidence: 99%

Refining the pneumococcal competence regulon by RNA-sequencing

Slager

Aprianto

Veening

2018

Preprint

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Streptococcus pneumoniae (the pneumococcus) is a mostly harmless human commensal found in the nasopharynx. However, when the pneumococcus leaves the nasopharynx and ends up in other niches, it may cause severe diseases, such as sepsis, pneumonia and meningitis (1). Especially among individuals with a weakened immune system, these diseases lead to over a million deaths per year (2). Although both vaccination and antibiotic therapy have been used successfully for, respectively, prevention and treatment of infections, the pneumococcus remains a threat to human health. This persistence is largely due to the remarkable genomic plasticity of the pneumococcus, allowing the acquisition of antibiotic resistance and evasion of the host immune response. Horizontal gene transfer, underlying the vast majority of such diversification strategies, is facilitated by pneumococcal competence. The competent state allows cells to take up exogenous DNA and integrate it into their own genome (i.e. transformation). During competence, various functionalities are activated, including DNA repair, bacteriocin production and several stress-response regulons (3, 4). This diversity of activated functions is relevant in light of the fact that a broad spectrum of antimicrobial compounds (causing various forms of stress) can actually induce competence development (5-7), through at least three distinct mechanisms: HtrA substrate ABSTRACT Competence for genetic transformation allows the opportunistic human pathogen Streptococcus pneumoniae to take up exogenous DNA for incorporation into its own genome. This ability may account for the extraordinary genomic plasticity of this bacterium, leading to antigenic variation, vaccine escape, and the spread of antibiotic resistance markers. The competence system has been thoroughly studied and its regulation is well-understood. Additionally, over the last decade, several stress factors have been shown to trigger the competent state, leading to the activation of several stress response regulons. The arrival of next-generation sequencing techniques allowed us to update the competence regulon, the latest report of which still depended on DNA microarray technology. Enabled by the availability of an up-to-date genome annotation, including transcript boundaries, we assayed time-dependent expression of all annotated features in response to competence induction, were able to identify the affected promoters and produced a more complete overview of the various regulons activated during competence. We show that 4% of all annotated genes are under direct control of competence regulators ComE and ComX, while the expression of a total of up to 17% of all genes is, either directly or indirectly, affected. Among the affected genes are various small RNAs with an as-of-yet unknown function. Besides the ComE and ComX regulons, we were also able to refine the CiaR, VraR (LiaR) and BlpR regulons, underlining the strength of combining RNA-seq with a well-annotated genome.

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“…Together, these genes are usually referred to as essential com genes (23). Competence is also regulated by the CiaRH two-component system through the serine protease HtrA (26,27) and noncoding small RNA (28,29). HtrA inhibits the activation of the competence system (27).…”

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confidence: 99%

Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence

et al. 2016

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h Natural genetic transformation of Streptococcus pneumoniae, an important human pathogen, mediates horizontal gene transfer for the development of drug resistance, modulation of carriage and virulence traits, and evasion of host immunity. Transformation frequency differs greatly among pneumococcal clinical isolates, but the molecular basis and biological importance of this interstrain variability remain unclear. In this study, we characterized the transformation frequency and other associated phenotypes of 208 S. pneumoniae clinical isolates representing at least 30 serotypes. While the vast majority of these isolates (94.7%) were transformable, the transformation frequency differed by up to 5 orders of magnitude between the least and most transformable isolates. The strain-to-strain differences in transformation frequency were observed among many isolates producing the same capsule types, indicating no general association between transformation frequency and serotype. However, a statistically significant association was observed between the levels of transformation and colonization fitness/virulence in the hypertransformable isolates. Although nontransformable mutants of all the selected hypertransformable isolates were significantly attenuated in colonization fitness and virulence in mouse infection models, such mutants of the strains with relatively low transformability had no or marginal fitness phenotypes under the same experimental settings. This finding strongly suggests that the pneumococci with high transformation capability are "addicted" to a "hypertransformable" state for optimal fitness in the human host. This work has thus provided an intriguing hint for further investigation into how the competence system impacts the fitness, virulence, and other transformation-associated traits of this important human pathogen. Streptococcus pneumoniae (the pneumococcus) is a commensal in the upper airway of humans and an opportunistic pathogen for numerous infections, including pneumonia, otitis media, and meningitis (1). Genetic plasticity of S. pneumoniae mediated by horizontal gene transfer is a primary driving force behind the success of this pathogen in its adaptation to the increasingly hostile environment in humans, the only known natural host (2). S. pneumoniae is capable of horizontal gene transfer via transduction, transformation, conjugation, and specialized transduction (or pseudotransduction) (3). Natural genetic transformation, referred to as natural transformation herein, alters the bacterial genome via uptake of foreign DNA and subsequent integration of new sequences into recipient genomes by homologous recombination (4). Although natural transformation appears to be the sole mechanism of transferring chromosomal DNA in S. pneumoniae, conjugation mobilizes the transfer of integrative and conjugative elements (ICEs) between pneumococcal cells or between S. pneumoniae and other Gram-positive bacteria (3).Natural transformation has been attributed to the acquisition of exogenous genes for immune ev...

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Control of competence by related non-coding csRNAs in Streptococcus pneumoniae R6

Cited by 29 publications

References 48 publications

Grad‐seq in a Gram‐positive bacterium reveals exonucleolytic sRNA activation in competence control

Grad‐seq in a Gram‐positive bacterium reveals exonucleolytic sRNA activation in competence control

Refining the pneumococcal competence regulon by RNA-sequencing

Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence

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