Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>

ABSTRACT Recent studies have established the fact that multiple members of the Rgg family of transcriptional regulators serve as key components of quorum sensing (QS) pathways that utilize peptides as intercellular signaling molecules. We previously described a novel QS system in Streptococcus pyoge...

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Autores principales:	Breah LaSarre, Chaitanya Aggarwal, Michael J. Federle
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a53a1e834efc499793f25cb2cf372e47
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spelling	oai:doaj.org-article:a53a1e834efc499793f25cb2cf372e472021-11-15T15:39:11ZAntagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>10.1128/mBio.00333-122150-7511https://doaj.org/article/a53a1e834efc499793f25cb2cf372e472012-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00333-12https://doaj.org/toc/2150-7511ABSTRACT Recent studies have established the fact that multiple members of the Rgg family of transcriptional regulators serve as key components of quorum sensing (QS) pathways that utilize peptides as intercellular signaling molecules. We previously described a novel QS system in Streptococcus pyogenes which utilizes two Rgg-family regulators (Rgg2 and Rgg3) that respond to neighboring signaling peptides (SHP2 and SHP3) to control gene expression and biofilm formation. We have shown that Rgg2 is a transcriptional activator of target genes, whereas Rgg3 represses expression of these genes, and that SHPs function to activate the QS system. The mechanisms by which Rgg proteins regulate both QS-dependent and QS-independent processes remain poorly defined; thus, we sought to further elucidate how Rgg2 and Rgg3 mediate gene regulation. Here we provide evidence that S. pyogenes employs a unique mechanism of direct competition between the antagonistic, peptide-responsive proteins Rgg2 and Rgg3 for binding at target promoters. The highly conserved, shared binding sites for Rgg2 and Rgg3 are located proximal to the −35 nucleotide in the target promoters, and the direct competition between the two regulators results in concentration-dependent, exclusive occupation of the target promoters that can be skewed in favor of Rgg2 in vitro by the presence of SHP. These results suggest that exclusionary binding of target promoters by Rgg3 may prevent Rgg2 binding under SHP-limiting conditions, thereby preventing premature induction of the quorum sensing circuit. IMPORTANCE Rgg-family transcriptional regulators are widespread among low-G+C Gram-positive bacteria and in many cases contribute to bacterial physiology and virulence. Only recently was it discovered that several Rgg proteins function in cell-to-cell communication (quorum sensing [QS]) via direct interaction with signaling peptides. The mechanism(s) by which Rgg proteins mediate regulation is poorly understood, and further insight into Rgg function is anticipated to be of great importance for the understanding of both regulatory-network architecture and intercellular communication in Rgg-containing species. The results of this study on the Rgg2/3 QS circuit of S. pyogenes demonstrate that DNA binding of target promoters by the activator Rgg2 is directly inhibited by competitive binding by the repressor Rgg3, thereby preventing transcriptional activation of the target genes and premature induction of the QS circuit. This is a unique regulatory mechanism among Rgg proteins and other peptide-responsive QS regulators.Breah LaSarreChaitanya AggarwalMichael J. FederleAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 6 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Breah LaSarre Chaitanya Aggarwal Michael J. Federle Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
description	ABSTRACT Recent studies have established the fact that multiple members of the Rgg family of transcriptional regulators serve as key components of quorum sensing (QS) pathways that utilize peptides as intercellular signaling molecules. We previously described a novel QS system in Streptococcus pyogenes which utilizes two Rgg-family regulators (Rgg2 and Rgg3) that respond to neighboring signaling peptides (SHP2 and SHP3) to control gene expression and biofilm formation. We have shown that Rgg2 is a transcriptional activator of target genes, whereas Rgg3 represses expression of these genes, and that SHPs function to activate the QS system. The mechanisms by which Rgg proteins regulate both QS-dependent and QS-independent processes remain poorly defined; thus, we sought to further elucidate how Rgg2 and Rgg3 mediate gene regulation. Here we provide evidence that S. pyogenes employs a unique mechanism of direct competition between the antagonistic, peptide-responsive proteins Rgg2 and Rgg3 for binding at target promoters. The highly conserved, shared binding sites for Rgg2 and Rgg3 are located proximal to the −35 nucleotide in the target promoters, and the direct competition between the two regulators results in concentration-dependent, exclusive occupation of the target promoters that can be skewed in favor of Rgg2 in vitro by the presence of SHP. These results suggest that exclusionary binding of target promoters by Rgg3 may prevent Rgg2 binding under SHP-limiting conditions, thereby preventing premature induction of the quorum sensing circuit. IMPORTANCE Rgg-family transcriptional regulators are widespread among low-G+C Gram-positive bacteria and in many cases contribute to bacterial physiology and virulence. Only recently was it discovered that several Rgg proteins function in cell-to-cell communication (quorum sensing [QS]) via direct interaction with signaling peptides. The mechanism(s) by which Rgg proteins mediate regulation is poorly understood, and further insight into Rgg function is anticipated to be of great importance for the understanding of both regulatory-network architecture and intercellular communication in Rgg-containing species. The results of this study on the Rgg2/3 QS circuit of S. pyogenes demonstrate that DNA binding of target promoters by the activator Rgg2 is directly inhibited by competitive binding by the repressor Rgg3, thereby preventing transcriptional activation of the target genes and premature induction of the QS circuit. This is a unique regulatory mechanism among Rgg proteins and other peptide-responsive QS regulators.
format	article
author	Breah LaSarre Chaitanya Aggarwal Michael J. Federle
author_facet	Breah LaSarre Chaitanya Aggarwal Michael J. Federle
author_sort	Breah LaSarre
title	Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_short	Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_full	Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_fullStr	Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_full_unstemmed	Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_sort	antagonistic rgg regulators mediate quorum sensing via competitive dna binding in <named-content content-type="genus-species">streptococcus pyogenes</named-content>
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/a53a1e834efc499793f25cb2cf372e47
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Antagonistic Rgg Regulators Mediate Quorum Sensing via Competitive DNA Binding in <named-content content-type="genus-species">Streptococcus pyogenes</named-content>

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