The CovR regulatory network drives the evolution of Group B Streptococcus virulence
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PROVIDER: PRJNA663852 | ENA |
REPOSITORIES: ENA
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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:Virulence of the neonatal pathogen Group B Streptococcus is under the control of the master regulator CovR. Inactivation of CovR is associated with large-scale transcriptome remodeling and impairs almost every step of the interaction between the pathogen and the host. However, transcriptome analyses suggested a plasticity of the CovR signaling pathway in clinical isolates leading to phenotypic heterogeneity in the bacterial population. In this study, we characterized the CovR regulatory network in a strain representative of the CC-17 hypervirulent lineage responsible of the majority of neonatal meningitis. Transcriptome and genome-wide binding analysis reveal the architecture of the CovR network characterized by the direct repression of a large array of virulence-associated genes and the extent of co-regulation at specific loci. Comparative functional analysis of the signaling network links strain-specificities to the regulation of the pan-genome, including the two specific hypervirulent adhesins and horizontally acquired genes, to mutations in CovR-regulated promoters, and to variability in CovR activation by phosphorylation. This regulatory adaptation occurs at the level of genes, promoters, and of CovR itself, and allows to globally reshape the expression of virulence genes. Overall, our results reveal the direct, coordinated, and strain-specific regulation of virulence genes by the master regulator CovR and suggest that the intra-species evolution of the signaling network is as important as the expression of specific virulence factors in the emergence of clone associated with specific diseases.
| S-EPMC8448333 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-08-23 | GSE158049 | GEO
Project description:We report the characterization of the major regulator of virulence gene expression (CovR) in Group B Streptococcus. The ChIP-seq experiments define the binding of CovR on the chromosome of the BM110 strain, a representative of the hypervirulent GBS lineage responsible of neonatal meningitis. Regulatory evolution of CovR signaling was investigated by comparing ChIP-seq done in parallel in a second GBS clinical isolate (NEM316) not belonging to the hypervirulent lineage.
2021-08-23 | GSE158046 | GEO
Project description:The control of virulence two-component gene regulatory system (CovRS) is critical to the pathogenesis of many medically important streptococci. In emm1 group A streptococci (GAS), CovR directly binds the promoters of numerous GAS virulence factor encoding genes. Elimination of CovS phosphatase activity increases CovR phosphorylation (CovR~P) levels and abrogates GAS virulence. Given the emm type-specific diversity of CovRS function, herein we used ChIP-seq to define global CovR DNA occupancy in the wild-type emm3 strain MGAS10870 (medium CovR~P) and its CovS phosphatase-negative derivative 10870-CovS-T284A (high CovR~P). In the wild-type emm3 strain, 89% of the previously identified emm1 CovR binding sites present in the emm3 genome were also enriched; additionally, we ascertained unique CovR binding, primarily to genes in mobile genetic elements and other sites of inter-strain chromosomal differences. Elimination of phosphatase activity specifically increased CovR occupancy at the promoters of a broad array of CovR repressed virulence factor encoding genes, including those encoding the key GAS regulator Mga and M protein. However, a limited number of promoters had augmented enrichment at low CovR~P levels. Differential motif searches using sequences enriched at high vs. low CovR~P levels revealed two distinct binding patterns. At high CovR~P, a pseudo-palindromic AT-rich consensus sequence consistent with CovR binding as a dimer was determined. Conversely, sequences specifically enriched at low CovR~P contained isolated “ATTARA” motifs suggesting an interaction with a monomer. These data extend understanding of global CovR DNA occupancy beyond emm1 GAS and provide a mechanism for previous observations regarding hypovirulence induced by CovS phosphatase abrogation.
2023-05-31 | GSE230870 | GEO
Project description:To define the transcriptional response associated to a CovR inactivation we performed RNA-Seq in GBS strains BM110 and NEM316. We used mutants in which CovR is inactivated following a two base-pairs chromosomal substitution (AT->CC) resulting in the translation of a CovRD53A variant unable to be phosphorylated by the histidine kinase CovS. We also used a ∆covR mutant in strain BM110 in which the covR sequence is deleted from the chromosome.
2021-08-23 | GSE158047 | GEO
Project description:The goal of this study were to compare the transcriptoms of CcpA and CovR in group A Streptococcus. Isogenic mutant strains were created in which CcpA and CovR were inactivated alone and in combination. The transcriptomes of the four strains (wild-type, CcpA mutant, CovR mutant, and ccpA-covR double mutant) were then compared.
2010-03-01 | GSE20212 | GEO
Project description:The goal of this study were to compare the transcriptoms of CcpA and CovR in group A Streptococcus. Isogenic mutant strains were created in which CcpA and CovR were inactivated alone and in combination. The transcriptomes of the four strains (wild-type, CcpA mutant, CovR mutant, and ccpA-covR double mutant) were then compared. Four biological replicates of each strain were grown to the mid-exponential and stationary phases of growth in THY. Cells were harvested, RNA isolated, and converted to cDNA. cDNA was hybridized to a custom-made Affymetrix GeneChip that contains 100% of the ORFs of the wild-type strain MGAS2221.
2010-05-06 | E-GEOD-20212 | biostudies-arrayexpress
Project description:In this study we sought to determine the effects of single amino acid replacements in the control of virulence regulatory (CovR) regulatory protein on group A streptococcal global gene expression. We compared the transcriptomes of the serotype M3 strain MGAS10870 with four derivative strains: 1) a strain in which CovR had been completely inactivated (CovR knockout); 2) a strain in which the Arg 144 amino acid was changed to a cysteine (CovR-R144C); 3) a strain in which the Arg 158 amino acid was changed to a cysteine (CovR-R158C); and 4) a strain in which the the Asn 193 amino acid was changed to an isoleucine (CovR-N193I). Duplicate samples of each strain were grown to mid-exponential phase and the relative transcriptomes were compared using an Affymetrix GeneChipl.
2011-11-01 | E-GEOD-32106 | biostudies-arrayexpress
Project description:In this study we sought to determine the effects of single amino acid replacements in the control of virulence regulatory (CovR) regulatory protein on group A streptococcal global gene expression.
2011-11-01 | GSE32106 | GEO