| Title: | Competence shut-off by intracellular pheromone degradation in salivarius streptococci |
| Author(s): | Knoops A; Ledesma-Garcia L; Waegemans A; Lamontagne M; Decat B; Degand H; Morsomme P; Soumillion P; Delvigne F; Hols P; |
| Address: | "Louvain Institute of Biomolecular Science and Technology, Universite catholique de Louvain, Louvain-La-Neuve, Belgium. Microbial Processes and Interactions, TERRA Research and Teaching Center, Gembloux Agro-Bio Tech, University of Liege, Gembloux, Belgium" |
| DOI: | 10.1371/journal.pgen.1010198 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "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" |
| Keywords: | "*Bacterial Proteins/metabolism DNA Transformation Competence/genetics Gene Expression Regulation, Bacterial Humans Peptides/genetics Pheromones/genetics/metabolism *Regulon/genetics Signal Transduction/genetics;" |
| Notes: | "MedlineKnoops, Adrien Ledesma-Garcia, Laura Waegemans, Alexandra Lamontagne, Morgane Decat, Baptiste Degand, Herve Morsomme, Pierre Soumillion, Patrice Delvigne, Frank Hols, Pascal eng Research Support, Non-U.S. Gov't 2022/05/26 PLoS Genet. 2022 May 25; 18(5):e1010198. doi: 10.1371/journal.pgen.1010198. eCollection 2022 May" |
