Identification of Distinct Impacts of CovS Inactivation on the Transcriptome of Acapsular Group A Streptococci
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ABSTRACT:
ORGANISM(S): Streptococcus pyogenes
PROVIDER: GSE230158 | GEO | 2023/04/25
REPOSITORIES: GEO
Similar Datasets
Project description:We sought to determine how single amino acid changes in the active site of CovS autophosphorylation and subsequent phosphorylation of the response regulator CovR affect the gene expression profile of group A streptococcus There were 6 strains analyzed, each in quadruplicate replicates: 1) wild-type GAS; 2) covS deletion strain; 3) covS with alanine at AA 280; 4) covS with valine at AA 281; 5) covS with valine at AA 284; 6) covS with alanine at AA 457
2015-01-24 | E-GEOD-65226 | biostudies-arrayexpress
Project description:Identification of Distinct Impacts of CovS Inactivation on the Transcriptome of Acapsular Group A Streptococci
| PRJNA957761 | ENA
Project description:We investigated the covS-regulation of S. pyogenes in a hypervirulent M23 strain using RNA-sequencing. The differential gene expression comparison between the covS- mutant and isogenic wild type covS+ identified altered expression of 349 (18%) genes, including a broad spectrum of virulence genes and diverse metabolic genes. The data showed that the strain achieved hypervirulence by enhancing the expression of genes responsible for invasiveness and antiphagocytosis (i.e., hasABC), by abrogating the expression of toxic genes (i.e., speB), and by compromising gene products with dispensable functions (i.e., sfb1). Meanwhile, we found that covS also regulated diverse kinds of metabolic genes that maximized nutrient utilization and energy metabolism during growth and dissemination. From constructing a genome-scale metabolic model, we identified fourteen non-redundant metabolic gene modules, which constitute unique sources for specific nutrients. These genes were probably essential for pathogen growth and virulence. In general, this study provided quantitative transcriptomic signatures of the covS regulation in a hypervirulent S. pyogenes strain and addressed major aspects of the covS-modulated virulent mechanisms. Examination of expression profiling of covS- mutant strain and isogenic wild type covS+ at different growth stages.
2015-08-05 | E-GEOD-67533 | biostudies-arrayexpress
Project description:We investigated the covS-regulation of S. pyogenes in a hypervirulent M23 strain using RNA-sequencing. The differential gene expression comparison between the covS- mutant and isogenic wild type covS+ identified altered expression of 349 (18%) genes, including a broad spectrum of virulence genes and diverse metabolic genes. The data showed that the strain achieved hypervirulence by enhancing the expression of genes responsible for invasiveness and antiphagocytosis (i.e., hasABC), by abrogating the expression of toxic genes (i.e., speB), and by compromising gene products with dispensable functions (i.e., sfb1). Meanwhile, we found that covS also regulated diverse kinds of metabolic genes that maximized nutrient utilization and energy metabolism during growth and dissemination. From constructing a genome-scale metabolic model, we identified fourteen non-redundant metabolic gene modules, which constitute unique sources for specific nutrients. These genes were probably essential for pathogen growth and virulence. In general, this study provided quantitative transcriptomic signatures of the covS regulation in a hypervirulent S. pyogenes strain and addressed major aspects of the covS-modulated virulent mechanisms.
2015-08-05 | GSE67533 | GEO
Project description:Group A Streptococcus (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1UK lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections, however the basis for its evolutionary success is not yet fully understood. During the transition to systemic disease, the M1 serotype is known to give rise to spontaneous mutations in the CovRS two-component transcriptional regulation system that confer a fitness advantage during invasive infections. Mutations that inactivate CovS function result in the de-repression of key GAS virulence factors such as Streptolysin O (SLO), a pore-forming toxin and major trigger of inflammasome/interleukin-1-dependent inflammation. Conversely, expression of the streptococcal cysteine protease SpeB, which is required during initial stages of colonisation and onset of invasive disease, is typically lost in such mutants. In this study, we identified and characterised a novel covS mutation detected in three separate invasive M1UK isolates. The resulting CovSAla318Val mutation caused a significant upregulation of SLO resulting in increased inflammasome activation in human THP-1 macrophages, indicating an enhanced inflammatory potential. Surprisingly, SpeB production was unaffected. Site-directed mutagenesis was performed to assess the impact of this mutation on virulence and global gene expression. We found that the CovSAla318Val mutation led to subtle, virulence-specific changes of the CovRS regulon compared to previously characterised covS mutations, highlighting an unappreciated level of complexity in CovRS-dependent gene regulation. Continued longitudinal surveillance is warranted to determine whether this novel covS mutation will expand in the M1UK lineage.
2024-10-28 | GSE280498 | GEO
Project description:Group A streptococcal (GAS) strains causing severe, invasive infections often have mutations in the control of virulence two-component regulatory system (CovRS) which represses capsule production, and high-level capsule production is considered critical to the GAS hypervirulent phenotype. Additionally, based on studies in emm1 GAS, hyperencapsulation is thought to limit transmission of CovRS-mutated strains by reducing GAS adherence to mucosal surfaces. It has recently been identified that about 30% of invasive GAS strains lacks capsule, but there are limited data regarding the impact of CovS inactivation in such acapsular strains. Using publicly available complete genomes (n = 2,455) of invasive GAS strains, we identified similar rates of CovRS inactivation and limited evidence for transmission of CovRS-mutated isolates for both encapsulated and acapsular emm types. Relative to encapsulated GAS, CovS transcriptomes of the prevalent acapsular emm types emm28, emm87, and emm89 revealed unique impacts such as increased transcript levels of genes in the emm/mga region along with decreased transcript levels of pilus operon-encoding genes and the streptokinase-encoding gene ska. CovS inactivation in emm87 and emm89 strains, but not emm28, increased GAS survival in human blood. Moreover, CovS inactivation in acapsular GAS reduced adherence to host epithelial cells. These data suggest that the hypervirulence induced by CovS inactivation in acapsular GAS follows distinct pathways from the better studied encapsulated strains and that factors other than hyperencapsulation may account for the lack of transmission of CovRS-mutated strains. IMPORTANCE Devastating infections due to group A streptococci (GAS) tend to occur sporadically and are often caused by strains that contain mutations in the control of virulence regulatory system (CovRS). In well-studied emm1 GAS, the increased production of capsule induced by CovRS mutation is considered key to both hypervirulence and limited transmissibility by interfering with proteins that mediate attachment to eukaryotic cells. Herein, we show that the rates of covRS mutations and genetic clustering of CovRS-mutated isolates are independent of capsule status. Moreover, we found that CovS inactivation in multiple acapsular GAS emm types results in dramatically altered transcript levels of a diverse array of cell-surface protein-encoding genes and a unique transcriptome relative to encapsulated GAS. These data provide new insights into how a major human pathogen achieves hypervirulence and indicate that factors other than hyperencapsulation likely account for the sporadic nature of the severe GAS disease.
| S-EPMC10470059 | biostudies-literature
Project description:We sought to determine how single amino acid changes in the active site of CovS autophosphorylation and subsequent phosphorylation of the response regulator CovR affect the gene expression profile of group A streptococcus
2015-01-24 | GSE65226 | GEO
Project description:Expression of the extensive arsenal of virulence factors by Streptococcus pyogenes are controlled by many regulators, of which covR/S is one of the best characterized and can influence ~15% of the genome. Animal models have established that mutants of CovR/S arise spontaneously in vivo resulting in highly invasive organisms. We analyzed a pharyngeal and a blood isolate of S. pyogenes recovered from the same individual 13 days apart. The two isolates varied in many phenotypic properties including speB production, which were reflected in transcriptome analyses. Pulsed field gel electrophoresis, multilocus sequence typing, and partial sequencing of some key genes failed to show any differences except for an 11-base insert in the covS gene in the blood isolate. These results showing that pharyngeal and blood isolates from a single individual which differ by a simple insertion, provide evidence for the model that regulatory gene mutations allow S. pyogenes to invade different niches in the body. A chip study using total RNA recovered from two separate wild-type cultures of group A Streptococcus, Streptococcus pyogenes UH322 and UH328. Each chip measures the expression level of 1865 genes replicated twice from 7 fully sequenced strains of Streptococcus pyogenes (M1_GAS NC_002737; MGAS10394 NC_006086; MGAS315 NC_004070; MGAS5005 NC_007297; MGAS6180 NC_007296; MGAS8232 NC_003485; SSI-1 NC_004606 with fourteen 24-mer probe pairs (PM/MM) per gene, with three-fold technical redundancy.
2010-05-01 | E-GEOD-21316 | biostudies-arrayexpress
Project description:Background: Streptococcus dysgalactiae subsp. equisimilis (SDSE), similar to Lancefield group A Streptococcus pyogenes (GAS), causes invasive diseases such as life-threatening streptococcal toxic shock syndrome (STSS). Despite their similar genome sequences, SDSE lacks several important virulence factors of GAS, suggesting that SDSE has specific disease-causing systems. Using microarray analysis, we analyzed SDSE for specific transcriptional regulatory systems involved in stress responses, such as the LytSR/LrgAB system, and their transcriptional profiles under stress conditions. Methods: Transcriptional profiling was performed using microarrays to test the effects of eight antibiotics and five growth conditions. These findings were compared with those obtained during intraperitoneal infection in mice. Results: Genes encoding LrgAB, which modulates the murein hydrolase activity of CidAB and inhibits autolysis in Staphylococcus aureus, were upregulated by exposure to antibacterial agents, phosphate buffered saline (PBS) and stationary phase conditions and during intraperitoneal infection in mice. Starvation and anaerobic conditions stimulated the expression of the streptolysin S operon and polysaccharide lyases in SDSE. Catabolite-responsive elements (cre) were present in the promoter regions of these genes, suggesting that carbon catabolite repression (CCR) is involved in regulating SDSE virulence factors. Comparative genome analysis showed the presence in SDSE of the LytSR/LrgAB system and an additional sigma factor (SDEG_0623), both of which were absent from the GAS genome. Conclusions: These results suggest that the LytSR/LrgAB and CCR play important roles in bacterial resistance to stress microenvironments. Microarray data also indicated that starvation and low oxygen tension partly mimic the microenvironment present during invasive diseases.
2016-12-31 | GSE50213 | GEO
Project description:Group A streptococci (GAS) may engage different sets of virulence strategies, depending on the site of infection and host context. We previously isolated 2 phenotypic variants of a globally disseminated M1T1 GAS clone: a virulent wild-type (WT) strain, characterized by a SpeB(+)/SpeA(-)/Sda1(low) phenotype, and a hypervirulent animal-passaged (AP) strain, better adapted to survive in vivo, with a SpeB(-)/SpeA(+)/Sda1(high) phenotype. This AP strain arises in vivo due to the selection of bacteria with mutations in covS, the sensor part of a key 2-component regulatory system, CovR/S. To determine whether covS mutations explain the hypervirulence of the AP strain, we deleted covS from WT bacteria (DeltaCovS) and were able to simulate the hypervirulence and gene expression phenotype of naturally selected AP bacteria. Correction of the covS mutation in AP bacteria reverted them back to the WT phenotype. Our data confirm that covS plays a direct role in regulating GAS virulence.
2010-09-22 | GSE24246 | GEO