The emerging role of bacterial regulatory RNAs in disease

Eichner, Hannes; Karlsson, Jens; Loh, Edmund

doi:10.1016/j.tim.2022.03.007

Cited by 23 publications

(14 citation statements)

References 87 publications

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“…The attB OXC site at which ϕOXC141 inserts was originally identified as intergenic [ 32 ], but has subsequently been shown to be within the ccnC gene, which generates the antisense non-coding RNA csRNA3 [ 78 ]. This is one of the ccnA - E genes in S. pneumoniae , encoding csRNA1-5, all of which target the comC gene [ 60 ], likely by either blocking its translation [ 60 ], or triggering degradation of the comC transcript through forming a double-stranded RNA complex [ 81 ]. The comC gene encodes the protein that is processed to generate competence-stimulating peptide (CSP), an autoinducing quorum-sensing pheromone necessary for pneumococci to undergo efficient transformation [ 82 ].…”

Section: Resultsmentioning

confidence: 99%

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

et al. 2022

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Background The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180). Methods A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain’s evolution. Results GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage ϕOXC141. Prior to the introduction of PCV13, this clade’s composition shifted towards a ϕOXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also ϕOXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the ~100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage ϕOXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in ~30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation. Conclusion This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics.

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Section: Resultsmentioning

confidence: 99%

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

et al. 2022

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“…RNAs regulate the target gene expressions from different gene loci through affecting mRNA stability (Eichner et al, 2022). In grampositive bacteria, trans-regulatory RNA often functions in the presence of chaperones, such as Hfq, CsrA, ProQ, and so on (Papenfort & Vogel, 2010).…”

Section: Trans-regulatory Rnasmentioning

confidence: 99%

“…The fundamental roles of sRNA in the pathogenicity of bacteria have been noticed and recognized by researchers (Eichner et al, 2022). However, our current knowledge to the enormous and mysterious riboregulators remains scarce.…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Small noncoding RNA in Streptococci: From regulatory functions to drug development

Yang

Wang

Liu

et al. 2023

Molecular Oral Microbiology

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Streptococci are a genus of gram‐positive coccus of spherical bacteria, including many commensal bacteria and opportunistic pathogens that threaten the public health system. Small noncoding RNAs (sRNAs) are a class of noncoding RNAs regulating gene expression via various regulatory mechanisms, which have been illustrated to play vital roles in regulations of virulence factor expressions. Recent advances in sequencing technology and bioinformatic analysis facilitated discovery of a myriad of sRNAs from pathogenic bacteria, revealing a variety of unique features that contribute to gene expressions and virulence regulations. Although various research studies have reported the regulatory functions of sRNAs in the virulence of bacterial species of the genus Streptococci, the common features of sRNAs in the pathogenesis of Streptococci remain unclear. This blocks the development of novel antistreptococcal antibiotics and antibacterial strategies. Here, we summarize the fundamental roles of Streptococcal sRNAs in pathogenic regulations, which advance mechanistic understanding of streptococcal infection associated diseases. Moreover, we discuss the prospects of sRNA acting as drug targets to combat bacterial antibiotic resistance.

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“…Being able to predict in given colonized individuals if they will contract infection and, if so, anticipating how severe the outcome will be should provide a substantial advance notification to set up the appropriate treatment. When human pathogens switch from colonization to infection, they reprogram their gene expression pattern to respond and adapt to the host defense mechanisms and to the multiple stresses encountered ( 15 ). Whereas a large number of toxins, transcription factors, and small RNAs (sRNAs) participate in S. aureus virulence ( 16 ), a breach in host immunity is fertile ground for staphylococcal infections.…”

Section: Introductionmentioning

confidence: 99%

Forecasting Staphylococcus aureus Infections Using Genome-Wide Association Studies, Machine Learning, and Transcriptomic Approaches

et al. 2022

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Predicting the outcome of bacterial colonization and infections, based on extensive genomic and transcriptomic data from a given pathogen, would be of substantial help for clinicians in treating and curing patients. In this report, genome-wide association studies and random forest algorithms have defined gene combinations that differentiate human from animal strains, colonization from diseases, and nonsevere from severe diseases, while it revealed the importance of IGRs and CDS, but not small RNAs (sRNAs), in anticipating an outcome.

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The emerging role of bacterial regulatory RNAs in disease

Cited by 23 publications

References 87 publications

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

Small noncoding RNA in Streptococci: From regulatory functions to drug development

Forecasting Staphylococcus aureus Infections Using Genome-Wide Association Studies, Machine Learning, and Transcriptomic Approaches

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