Competence shut-off by intracellular pheromone degradation in salivarius streptococci.
Competence for DNA transformation is a major strategy for bacterial adaptation and survival. Yet, this successful tactic is energy-consuming, shifts dramatically the metabolism, and transitory impairs the regular cell-cycle. In streptococci, complex regulatory pathways control competence deactivatio...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010198 |
| _version_ | 1828330054756597760 |
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| author | Adrien Knoops Laura Ledesma-García Alexandra Waegemans Morgane Lamontagne Baptiste Decat Hervé Degand Pierre Morsomme Patrice Soumillion Frank Delvigne Pascal Hols |
| author_facet | Adrien Knoops Laura Ledesma-García Alexandra Waegemans Morgane Lamontagne Baptiste Decat Hervé Degand Pierre Morsomme Patrice Soumillion Frank Delvigne Pascal Hols |
| author_sort | Adrien Knoops |
| collection | DOAJ |
| description | Competence for DNA transformation is a major strategy for bacterial adaptation and survival. Yet, this successful tactic is energy-consuming, shifts dramatically the metabolism, and transitory impairs the regular cell-cycle. In streptococci, complex regulatory pathways control competence deactivation to narrow its development to a sharp window of time, a process known as competence shut-off. Although characterized in streptococci whose competence is activated by the ComCDE signaling pathway, it remains unclear for those controlled by the ComRS system. In this work, we investigate competence shut-off in the major human gut commensal Streptococcus salivarius. Using a deterministic mathematical model of the ComRS system, we predicted a negative player under the control of the central regulator ComX as involved in ComS/XIP pheromone degradation through a negative feedback loop. The individual inactivation of peptidase genes belonging to the ComX regulon allowed the identification of PepF as an essential oligoendopeptidase in S. salivarius. By combining conditional mutants, transcriptional analyses, and biochemical characterization of pheromone degradation, we validated the reciprocal role of PepF and XIP in ComRS shut-off. Notably, engineering cleavage site residues generated ultra-resistant peptides producing high and long-lasting competence activation. Altogether, this study reveals a proteolytic shut-off mechanism of competence in the salivarius group and suggests that this mechanism could be shared by other ComRS-containing streptococci. |
| first_indexed | 2024-04-13T20:35:25Z |
| format | Article |
| id | doaj.art-618a4b468dc14f1181001305db9f3373 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-13T20:35:25Z |
| publishDate | 2022-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-618a4b468dc14f1181001305db9f33732022-12-22T02:31:04ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-05-01185e101019810.1371/journal.pgen.1010198Competence shut-off by intracellular pheromone degradation in salivarius streptococci.Adrien KnoopsLaura Ledesma-GarcíaAlexandra WaegemansMorgane LamontagneBaptiste DecatHervé DegandPierre MorsommePatrice SoumillionFrank DelvignePascal HolsCompetence for DNA transformation is a major strategy for bacterial adaptation and survival. Yet, this successful tactic is energy-consuming, shifts dramatically the metabolism, and transitory impairs the regular cell-cycle. In streptococci, complex regulatory pathways control competence deactivation to narrow its development to a sharp window of time, a process known as competence shut-off. Although characterized in streptococci whose competence is activated by the ComCDE signaling pathway, it remains unclear for those controlled by the ComRS system. In this work, we investigate competence shut-off in the major human gut commensal Streptococcus salivarius. Using a deterministic mathematical model of the ComRS system, we predicted a negative player under the control of the central regulator ComX as involved in ComS/XIP pheromone degradation through a negative feedback loop. The individual inactivation of peptidase genes belonging to the ComX regulon allowed the identification of PepF as an essential oligoendopeptidase in S. salivarius. By combining conditional mutants, transcriptional analyses, and biochemical characterization of pheromone degradation, we validated the reciprocal role of PepF and XIP in ComRS shut-off. Notably, engineering cleavage site residues generated ultra-resistant peptides producing high and long-lasting competence activation. Altogether, this study reveals a proteolytic shut-off mechanism of competence in the salivarius group and suggests that this mechanism could be shared by other ComRS-containing streptococci.https://doi.org/10.1371/journal.pgen.1010198 |
| spellingShingle | Adrien Knoops Laura Ledesma-García Alexandra Waegemans Morgane Lamontagne Baptiste Decat Hervé Degand Pierre Morsomme Patrice Soumillion Frank Delvigne Pascal Hols Competence shut-off by intracellular pheromone degradation in salivarius streptococci. PLoS Genetics |
| title | Competence shut-off by intracellular pheromone degradation in salivarius streptococci. |
| title_full | Competence shut-off by intracellular pheromone degradation in salivarius streptococci. |
| title_fullStr | Competence shut-off by intracellular pheromone degradation in salivarius streptococci. |
| title_full_unstemmed | Competence shut-off by intracellular pheromone degradation in salivarius streptococci. |
| title_short | Competence shut-off by intracellular pheromone degradation in salivarius streptococci. |
| title_sort | competence shut off by intracellular pheromone degradation in salivarius streptococci |
| url | https://doi.org/10.1371/journal.pgen.1010198 |
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