RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis

ABSTRACT Bacteria can communicate with each other to coordinate their biological functions at the population level. In a previous study, we described a cell-to-cell communication system in streptococci that involves a transcriptional regulator belonging to the Rgg family and short hydrophobic pepti...

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Autores principales:	David Pérez-Pascual, Philippe Gaudu, Betty Fleuchot, Colette Besset, Isabelle Rosinski-Chupin, Alain Guillot, Véronique Monnet, Rozenn Gardan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/79bb801b422948548522f2b6c4933f55
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spelling	oai:doaj.org-article:79bb801b422948548522f2b6c4933f552021-11-15T15:41:19ZRovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis10.1128/mBio.02306-142150-7511https://doaj.org/article/79bb801b422948548522f2b6c4933f552015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02306-14https://doaj.org/toc/2150-7511ABSTRACT Bacteria can communicate with each other to coordinate their biological functions at the population level. In a previous study, we described a cell-to-cell communication system in streptococci that involves a transcriptional regulator belonging to the Rgg family and short hydrophobic peptides (SHPs) that act as signaling molecules. Streptococcus agalactiae, an opportunistic pathogenic bacterium responsible for fatal infections in neonates and immunocompromised adults, has one copy of the shp/rgg locus. The SHP-associated Rgg is called RovS in S. agalactiae. In this study, we found that the SHP/RovS cell-to-cell communication system is active in the strain NEM316 of S. agalactiae, and we identified different partners that are involved in this system, such as the Eep peptidase, the PptAB, and the OppA1-F oligopeptide transporters. We also identified a new target gene controlled by this system and reexamined the regulation of a previously proposed target gene, fbsA, in the context of the SHP-associated RovS system. Furthermore, our results are the first to indicate the SHP/RovS system specificity to host liver and spleen using a murine model, which demonstrates its implication in streptococci virulence. Finally, we observed that SHP/RovS regulation influences S. agalactiae’s ability to adhere to and invade HepG2 hepatic cells. Hence, the SHP/RovS cell-to-cell communication system appears to be an essential mechanism that regulates pathogenicity in S. agalactiae and represents an attractive target for the development of new therapeutic strategies. IMPORTANCE Rgg regulators and their cognate pheromones, called small hydrophobic peptides (SHPs), are present in nearly all streptococcal species. The general pathways of the cell-to-cell communication system in which Rgg and SHP take part are well understood. However, many other players remain unidentified, and the direct targets of the system, as well as its link to virulence, remain unclear. Here, we identified the different players involved in the SHP/Rgg system in S. agalactiae, which is the leading agent of severe infections in human newborns. We have identified a direct target of the Rgg regulator in S. agalactiae (called RovS) and examined a previously proposed target, all in the context of associated SHP. For the first time, we have also demonstrated the implication of the SHP/RovS mechanism in virulence, as well as its host organ specificity. Thus, this cell-to-cell communication system may represent a future target for S. agalactiae disease treatment.David Pérez-PascualPhilippe GauduBetty FleuchotColette BessetIsabelle Rosinski-ChupinAlain GuillotVéronique MonnetRozenn GardanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 David Pérez-Pascual Philippe Gaudu Betty Fleuchot Colette Besset Isabelle Rosinski-Chupin Alain Guillot Véronique Monnet Rozenn Gardan RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis
description	ABSTRACT Bacteria can communicate with each other to coordinate their biological functions at the population level. In a previous study, we described a cell-to-cell communication system in streptococci that involves a transcriptional regulator belonging to the Rgg family and short hydrophobic peptides (SHPs) that act as signaling molecules. Streptococcus agalactiae, an opportunistic pathogenic bacterium responsible for fatal infections in neonates and immunocompromised adults, has one copy of the shp/rgg locus. The SHP-associated Rgg is called RovS in S. agalactiae. In this study, we found that the SHP/RovS cell-to-cell communication system is active in the strain NEM316 of S. agalactiae, and we identified different partners that are involved in this system, such as the Eep peptidase, the PptAB, and the OppA1-F oligopeptide transporters. We also identified a new target gene controlled by this system and reexamined the regulation of a previously proposed target gene, fbsA, in the context of the SHP-associated RovS system. Furthermore, our results are the first to indicate the SHP/RovS system specificity to host liver and spleen using a murine model, which demonstrates its implication in streptococci virulence. Finally, we observed that SHP/RovS regulation influences S. agalactiae’s ability to adhere to and invade HepG2 hepatic cells. Hence, the SHP/RovS cell-to-cell communication system appears to be an essential mechanism that regulates pathogenicity in S. agalactiae and represents an attractive target for the development of new therapeutic strategies. IMPORTANCE Rgg regulators and their cognate pheromones, called small hydrophobic peptides (SHPs), are present in nearly all streptococcal species. The general pathways of the cell-to-cell communication system in which Rgg and SHP take part are well understood. However, many other players remain unidentified, and the direct targets of the system, as well as its link to virulence, remain unclear. Here, we identified the different players involved in the SHP/Rgg system in S. agalactiae, which is the leading agent of severe infections in human newborns. We have identified a direct target of the Rgg regulator in S. agalactiae (called RovS) and examined a previously proposed target, all in the context of associated SHP. For the first time, we have also demonstrated the implication of the SHP/RovS mechanism in virulence, as well as its host organ specificity. Thus, this cell-to-cell communication system may represent a future target for S. agalactiae disease treatment.
format	article
author	David Pérez-Pascual Philippe Gaudu Betty Fleuchot Colette Besset Isabelle Rosinski-Chupin Alain Guillot Véronique Monnet Rozenn Gardan
author_facet	David Pérez-Pascual Philippe Gaudu Betty Fleuchot Colette Besset Isabelle Rosinski-Chupin Alain Guillot Véronique Monnet Rozenn Gardan
author_sort	David Pérez-Pascual
title	RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis
title_short	RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis
title_full	RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis
title_fullStr	RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis
title_full_unstemmed	RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis
title_sort	rovs and its associated signaling peptide form a cell-to-cell communication system required for <named-content content-type="genus-species">streptococcus agalactiae</named-content> pathogenesis
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/79bb801b422948548522f2b6c4933f55
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RovS and Its Associated Signaling Peptide Form a Cell-To-Cell Communication System Required for <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Pathogenesis

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