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Insert in CovS Gene Distinguishes a Pharyngeal and a Blood Isolate of Streptococcus pyogenes Found in the Same Individual.

ABSTRACT: 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.

ORGANISM(S): Streptococcus pyogenes

PROVIDER: GSE21316 | GEO | 2010/05/01

SECONDARY ACCESSION(S): PRJNA126325

REPOSITORIES: GEO

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Insert in CovS Gene Distinguishes a Pharyngeal and a Blood Isolate of Streptococcus pyogenes Found in the Same Individual.

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

Transcriptome comparison of M1T1 WT, AP and delta CovS strains

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

Transcriptome comparison of M1T1 WT, AP and delta CovS strains

2010-09-22 | E-GEOD-24246 | biostudies-arrayexpress

Transcriptome study of the covS-regulation of a Group A Streptococcus pyogenes M23ND

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

Transcriptome study of the covS-regulation of a Group A Streptococcus pyogenes M23ND

2015-08-05 | GSE67533 | GEO

CovS Inactivation Reduces CovR Promoter Binding at Diverse Virulence Factor Encoding Genes in Group A Streptococcus

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

Evaluation of covS polymorphisms on group A streptococcal global gene expression

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

Evaluation of covS polymorphisms on group A streptococcal global gene expression

2015-01-24 | GSE65226 | GEO

Identification of Distinct Impacts of CovS Inactivation on the Transcriptome of Acapsular Group A Streptococci

Project description:To determine the impact of CovS inactivation in acapsular GAS (Streptococcus pyogenes) strains

2023-04-25 | GSE230158 | GEO

Transcription profiling by array of abx1 deletion or over expression in Streptococcus agalactiae and comparision with the effect of CovS and CovR deletion

Project description:Analysis of the impact of the abx1 deletion or over expression on S. agalactaie transcription profile and comparision to the effect of CovS and CovR deletion on transcriptomic profile. Some of the mutants are gene_knock_out mutants, but in other strains we have tested the over expression of the Abx1 protein by an chromosomic overexpression, or by a plasmid overexpression. Chromosomic overexpression is indicated with a K and plasmid overexpression with a V.

2013-02-26 | E-MEXP-3703 | biostudies-arrayexpress

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