Competence in Streptococcus pneumoniae and Close Commensal Relatives: Mechanisms and Implications

Salvadori, Gabriela; Junges, Roger; Morrison, Donald A.; Petersen, Fernanda Cristina

doi:10.3389/fcimb.2019.00094

Cited by 80 publications

(77 citation statements)

References 74 publications

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“…TCS05 inhibits the competence state [18][19][20][21], and promotes pneumococcal resistance to certain antibiotics and other stressful conditions [20,[22][23][24]. TCS12 activates the genes associated with the competence state and natural transformation [25][26][27]. TCS02 (WalR/K), the only TCS essential for pneumococcal viability, is associated with cell wall peptidoglycan metabolism [28,29]; TCS03 (LiaR/S) senses cell wall damage and inhibits autolysis [30], TCS04 (PnpR/S) regulates uptake of inorganic phosphate [31,32]; TCS06 (CbpR/S) activates expression of choline-binding protein A or PspC [33,34]; TCS08 is involved in the cellobiose uptake [35], production of pilus-1 [16] and surface protein PavB [16]; TCS13 (BlpR/H) regulates the production of bacteriocins (pneumocins) [36][37][38].…”

Section: Plos Pathogensmentioning

confidence: 99%

Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems

Wang

et al. 2020

PLoS Pathog

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Streptococcus pneumoniae is well known for phase variation between opaque (O) and transparent (T) colonies within clonal populations. While the O variant is specialized in invasive infection (with a thicker capsule and higher resistance to host clearance), the T counterpart possesses a relatively thinner capsule and thereby higher airway adherence and colonization. Our previous study found that phase variation is caused by reversible switches of the "opaque ON-or-OFF" methylomes or methylation patterns of pneumococcal genome, which is dominantly driven by the PsrA-catalyzed inversions of the DNA methyltransferase hsdS genes. This study revealed that switch frequency between the O and T variants is regulated by five transcriptional response regulators (rr) of the two-component systems (TCSs). The mutants of rr06, rr08, rr09, rr11 and rr14 produced significantly fewer O and more T colonies. Further mutagenesis revealed that RR06, RR08, RR09 and RR11 enrich the O variant by modulating the directions of the PsrA-catalyzed inversion reactions. In contrast, the impact of RR14 (RitR) on phase variation is independent of PsrA. Consistently, SMRT sequencing uncovered significantly diminished "opaque ON" methylome in the mutants of rr06, rr08, rr09 and rr11 but not that of rr14. Lastly, the phosphorylated form of RR11 was shown to activate the transcription of comW and two sugar utilization systems that are necessary for maintenance of the "opaque ON" genotype and phenotype. This work has thus uncovered multiple novel mechanisms that balance pneumococcal epigenetic status and physiology.

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Section: Plos Pathogensmentioning

confidence: 99%

Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems

Wang

et al. 2020

PLoS Pathog

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“…Here, the application of Grad‐seq allowed us to identify the sedimentation profiles of thousands of S. pneumoniae transcripts and proteins simultaneously in a single experiment. We establish a use case for this complexome resource by uncovering an unexpected exonucleolytic stabilization of sRNAs in the competence regulon, a pathway essential for DNA uptake and important for pneumococcal virulence (Lin et al , ; Muschiol et al , ; Salvadori et al , ).…”

Section: Introductionmentioning

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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“…The phylogenetic relationship of both 16S rRNA and a core set of 136 genes indicated that this pathogen belongs to mitis group of Streptococcus (Kawamura et al, 1995;Richards et al, 2014). S. pneumoniae is capable of importing various genes including antimicrobial resistance genes via horizontal transfer from related species (Salvadori et al, 2019). In the United States of America, more than 30% of clinically isolated pneumococcal bacteria are resistant to one or more antibiotics (CDC, 2019).…”

Section: Introductionmentioning

confidence: 99%

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

et al. 2020

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Streptococcus pneumoniae is a major cause of pneumonia, sepsis, and meningitis. Previously, we identified a novel virulence factor by investigating evolutionary selective pressure exerted on pneumococcal choline-binding cell surface proteins. Herein, we focus on another pneumococcal cell surface protein. Cell wall-anchoring proteins containing the LPXTG motif are conserved in Gram-positive bacteria. Our evolutionary analysis showed that among the examined genes, nanA and bgaA had high proportions of codon that were under significant negative selection. Both nanA and bgaA encode a multi-functional glycosidase that aids nutrient acquisition in a glucose-poor environment, pneumococcal adherence to host cells, and evasion from host immunity. However, several studies have shown that the role of BgaA is limited in a mouse pneumonia model, and it remains unclear if BgaA affects pneumococcal pathogenesis in a mouse sepsis model. To evaluate the distribution and pathogenicity of bgaA, we performed phylogenetic analysis and intravenous infection assay. In both Bayesian and maximum likelihood phylogenetic trees, the genetic distances between pneumococcal bgaA was small, and the cluster of pneumococcal bgaA did not contain other bacterial orthologs except for a Streptococcus gwangjuense gene. Evolutionary analysis and BgaA structure indicated BgaA active site was not allowed to change. The mouse infection assay showed that the deletion of bgaA significantly reduced host mortality. These results indicated that both nanA and bgaA encode evolutionally conserved pneumococcal virulence factors and that molecular evolutionary analysis could be a useful alternative strategy for identification of virulence factors.

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Competence in Streptococcus pneumoniae and Close Commensal Relatives: Mechanisms and Implications

Cited by 80 publications

References 74 publications

Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems

Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems

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

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

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