RovS and its associated signaling peptide form a cell-to-cell communication system required for streptococcus agalactiae pathogenesis
| Autor: | Rozenn Gardan, Betty Fleuchot, David Pérez-Pascual, Alain Guillot, Philippe Gaudu, Véronique Monnet, Isabelle Rosinski-Chupin, Colette Besset |
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| Přispěvatelé: | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Marie Curie Intra European Fellowship for Career Development (IEF) 327146 DIM-ASTREA grant from the Region Ile-de-France ast11009, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
EXPRESSION
Cell signaling [SDV]Life Sciences [q-bio] Regulator Virulence ENTEROCOCCUS-FAECALIS Biology Protein Sorting Signals medicine.disease_cause GELATINASE THERMOPHILUS Microbiology GROUP-B STREPTOCOCCUS Streptococcus agalactiae FULL VIRULENCE Transcriptome 03 medical and health sciences Mice Bacterial Proteins Virology Streptococcal Infections RGG PROTEINS BACTERIA TRANSCRIPTOME COMPETENCE medicine Transcriptional regulation Animals Humans 030304 developmental biology 0303 health sciences Oligopeptide 030306 microbiology Gene Expression Regulation Bacterial QR1-502 3. Good health Cell biology Peptides Organ Specificity Research Article |
| Zdroj: | mBio mBio, American Society for Microbiology, 2015, 6 (1), ⟨10.1128/mBio.02306-14⟩ mBio, Vol 6, Iss 1 (2015) mBio, 2015, 6 (1), ⟨10.1128/mBio.02306-14⟩ mBio 1 (6), . (2015) |
| ISSN: | 2161-2129 2150-7511 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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