The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.

Group B Streptococcus (GBS), a common commensal of the female genital tract, is the leading cause of invasive infections in neonates. Expression of major GBS virulence factors, such as the hemolysin operon cyl, is regulated directly at the transcriptional level by the CovSR two-component system. Usi...

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Autores principales: Arnaud Firon, Asmaa Tazi, Violette Da Cunha, Sophie Brinster, Elisabeth Sauvage, Shaynoor Dramsi, Douglas T Golenbock, Philippe Glaser, Claire Poyart, Patrick Trieu-Cuot
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Acceso en línea:https://doaj.org/article/ce80e8fb70d14066acbdafaf34deea62
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spelling oai:doaj.org-article:ce80e8fb70d14066acbdafaf34deea622021-11-18T06:06:01ZThe Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.1553-73661553-737410.1371/journal.ppat.1003179https://doaj.org/article/ce80e8fb70d14066acbdafaf34deea622013-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23436996/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Group B Streptococcus (GBS), a common commensal of the female genital tract, is the leading cause of invasive infections in neonates. Expression of major GBS virulence factors, such as the hemolysin operon cyl, is regulated directly at the transcriptional level by the CovSR two-component system. Using a random genetic approach, we identified a multi-spanning transmembrane protein, Abx1, essential for the production of the GBS hemolysin. Despite its similarity to eukaryotic CaaX proteases, the Abx1 function is not involved in a post-translational modification of the GBS hemolysin. Instead, we demonstrate that Abx1 regulates transcription of several virulence genes, including those comprising the hemolysin operon, by a CovSR-dependent mechanism. By combining genetic analyses, transcriptome profiling, and site-directed mutagenesis, we showed that Abx1 is a regulator of the histidine kinase CovS. Overexpression of Abx1 is sufficient to activate virulence gene expression through CovS, overcoming the need for an additional signal. Conversely, the absence of Abx1 has the opposite effect on virulence gene expression consistent with CovS locked in a kinase-competent state. Using a bacterial two-hybrid system, direct interaction between Abx1 and CovS was mapped specifically to CovS domains involved in signal processing. We demonstrate that the CovSR two-component system is the core of a signaling pathway integrating the regulation of CovS by Abx1 in addition to the regulation of CovR by the serine/threonine kinase Stk1. In conclusion, our study reports a regulatory function for Abx1, a member of a large protein family with a characteristic Abi-domain, which forms a signaling complex with the histidine kinase CovS in GBS.Arnaud FironAsmaa TaziViolette Da CunhaSophie BrinsterElisabeth SauvageShaynoor DramsiDouglas T GolenbockPhilippe GlaserClaire PoyartPatrick Trieu-CuotPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 2, p e1003179 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Arnaud Firon
Asmaa Tazi
Violette Da Cunha
Sophie Brinster
Elisabeth Sauvage
Shaynoor Dramsi
Douglas T Golenbock
Philippe Glaser
Claire Poyart
Patrick Trieu-Cuot
The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.
description Group B Streptococcus (GBS), a common commensal of the female genital tract, is the leading cause of invasive infections in neonates. Expression of major GBS virulence factors, such as the hemolysin operon cyl, is regulated directly at the transcriptional level by the CovSR two-component system. Using a random genetic approach, we identified a multi-spanning transmembrane protein, Abx1, essential for the production of the GBS hemolysin. Despite its similarity to eukaryotic CaaX proteases, the Abx1 function is not involved in a post-translational modification of the GBS hemolysin. Instead, we demonstrate that Abx1 regulates transcription of several virulence genes, including those comprising the hemolysin operon, by a CovSR-dependent mechanism. By combining genetic analyses, transcriptome profiling, and site-directed mutagenesis, we showed that Abx1 is a regulator of the histidine kinase CovS. Overexpression of Abx1 is sufficient to activate virulence gene expression through CovS, overcoming the need for an additional signal. Conversely, the absence of Abx1 has the opposite effect on virulence gene expression consistent with CovS locked in a kinase-competent state. Using a bacterial two-hybrid system, direct interaction between Abx1 and CovS was mapped specifically to CovS domains involved in signal processing. We demonstrate that the CovSR two-component system is the core of a signaling pathway integrating the regulation of CovS by Abx1 in addition to the regulation of CovR by the serine/threonine kinase Stk1. In conclusion, our study reports a regulatory function for Abx1, a member of a large protein family with a characteristic Abi-domain, which forms a signaling complex with the histidine kinase CovS in GBS.
format article
author Arnaud Firon
Asmaa Tazi
Violette Da Cunha
Sophie Brinster
Elisabeth Sauvage
Shaynoor Dramsi
Douglas T Golenbock
Philippe Glaser
Claire Poyart
Patrick Trieu-Cuot
author_facet Arnaud Firon
Asmaa Tazi
Violette Da Cunha
Sophie Brinster
Elisabeth Sauvage
Shaynoor Dramsi
Douglas T Golenbock
Philippe Glaser
Claire Poyart
Patrick Trieu-Cuot
author_sort Arnaud Firon
title The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.
title_short The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.
title_full The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.
title_fullStr The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.
title_full_unstemmed The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus.
title_sort abi-domain protein abx1 interacts with the covs histidine kinase to control virulence gene expression in group b streptococcus.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/ce80e8fb70d14066acbdafaf34deea62
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