Back to Search
Start Over
The CovR regulatory network drives the evolution of Group B Streptococcus virulence.
- Source :
-
PLoS genetics [PLoS Genet] 2021 Sep 07; Vol. 17 (9), pp. e1009761. Date of Electronic Publication: 2021 Sep 07 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- 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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Bacterial Proteins genetics
Chromosomes, Bacterial
Genes, Bacterial
Host-Pathogen Interactions
Humans
Promoter Regions, Genetic
Prophages genetics
Streptococcus agalactiae genetics
Transcription, Genetic physiology
Virulence Factors genetics
Bacterial Proteins physiology
Gene Regulatory Networks
Streptococcus agalactiae pathogenicity
Virulence genetics
Virulence Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 17
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 34491998
- Full Text :
- https://doi.org/10.1371/journal.pgen.1009761