The CovR regulatory network drives the evolution of Group B Streptococcus virulence.

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...

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Autores principales:	Maria-Vittoria Mazzuoli, Maëlle Daunesse, Hugo Varet, Isabelle Rosinski-Chupin, Rachel Legendre, Odile Sismeiro, Myriam Gominet, Pierre Alexandre Kaminski, Philippe Glaser, Claudia Chica, Patrick Trieu-Cuot, Arnaud Firon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/40e97fe5090e4a2f8a87991050d2757f
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spelling	oai:doaj.org-article:40e97fe5090e4a2f8a87991050d2757f2021-12-02T20:03:21ZThe CovR regulatory network drives the evolution of Group B Streptococcus virulence.1553-73901553-740410.1371/journal.pgen.1009761https://doaj.org/article/40e97fe5090e4a2f8a87991050d2757f2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009761https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Virulence 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.Maria-Vittoria MazzuoliMaëlle DaunesseHugo VaretIsabelle Rosinski-ChupinRachel LegendreOdile SismeiroMyriam GominetPierre Alexandre KaminskiPhilippe GlaserClaudia ChicaPatrick Trieu-CuotArnaud FironPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009761 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Maria-Vittoria Mazzuoli Maëlle Daunesse Hugo Varet Isabelle Rosinski-Chupin Rachel Legendre Odile Sismeiro Myriam Gominet Pierre Alexandre Kaminski Philippe Glaser Claudia Chica Patrick Trieu-Cuot Arnaud Firon The CovR regulatory network drives the evolution of Group B Streptococcus virulence.
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.
format	article
author	Maria-Vittoria Mazzuoli Maëlle Daunesse Hugo Varet Isabelle Rosinski-Chupin Rachel Legendre Odile Sismeiro Myriam Gominet Pierre Alexandre Kaminski Philippe Glaser Claudia Chica Patrick Trieu-Cuot Arnaud Firon
author_facet	Maria-Vittoria Mazzuoli Maëlle Daunesse Hugo Varet Isabelle Rosinski-Chupin Rachel Legendre Odile Sismeiro Myriam Gominet Pierre Alexandre Kaminski Philippe Glaser Claudia Chica Patrick Trieu-Cuot Arnaud Firon
author_sort	Maria-Vittoria Mazzuoli
title	The CovR regulatory network drives the evolution of Group B Streptococcus virulence.
title_short	The CovR regulatory network drives the evolution of Group B Streptococcus virulence.
title_full	The CovR regulatory network drives the evolution of Group B Streptococcus virulence.
title_fullStr	The CovR regulatory network drives the evolution of Group B Streptococcus virulence.
title_full_unstemmed	The CovR regulatory network drives the evolution of Group B Streptococcus virulence.
title_sort	covr regulatory network drives the evolution of group b streptococcus virulence.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/40e97fe5090e4a2f8a87991050d2757f
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The CovR regulatory network drives the evolution of Group B Streptococcus virulence.

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