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: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: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
Project description:We performed CovR ChIP-seq analysis in the emm1 strain MGAS2221 and its CovS kinase deficient derivative strain 2221-CovS-E281A. We identified that CovR bound in the promoter regions of nearly all virulence factor encoding genes in the CovR regulon. Additionally, direct CovR binding was observed for numerous genes encoding proteins involved in amino acid metabolism, but we found limited direct CovR binding to genes encoding other transcriptional regulators. The consensus sequence AATRANAAAARVABTAAA was present in the promoters of genes directly regulated by CovR, and mutations of highly conserved positions within this motif relieved CovR repression of the hasA and M2221_0187 promoters. Analysis of strain 2221-CovS-E281A revealed that binding of CovR at repressed, but not activated, promoters is highly dependent on CovR~P state. CovR repressed virulence factor encoding genes could be grouped dependent on how variation in CovR~P differentially impacted DNA binding and gene transcript levels.
2022-01-03 | GSE192795 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE17767: Transcriptome comparison of Streptococcus pyogenes strain MGAS2221 with that of an isogenic PEL mutant GSE17789: Tiling microarray-based identification of small regulatory RNAs in the group A Streptococcus (GAS) Refer to individual Series
2009-08-25 | E-GEOD-17790 | biostudies-arrayexpress
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. A dye-swapped cyclic design was used in this study in order that each strain could be compared across all samples in silico. For each strain treated, 2 biological replicates were each analysed in dye-swapped technical replicates, giving a total of n=10 peplicates for each strain.
2010-09-22 | E-GEOD-24246 | biostudies-arrayexpress