Bacterial Proteins; Peptides; Pheromones; Bacterial Proteins/metabolism; DNA Transformation Competence/genetics; Gene Expression Regulation, Bacterial; Humans; Peptides/genetics; Pheromones/genetics/metabolism; Regulon/genetics; Signal Transduction/genetics
Abstract :
[en] 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.
Disciplines :
Microbiology
Author, co-author :
Knoops, Adrien ; Louvain Institute of Biomolecular Science and Technology, Université catholique
Ledesma-García, Laura ; Louvain Institute of Biomolecular Science and Technology, Université catholique
Waegemans, Alexandra ; Louvain Institute of Biomolecular Science and Technology, Université catholique
Lamontagne, Morgane; Louvain Institute of Biomolecular Science and Technology, Université catholique
Decat, Baptiste; Louvain Institute of Biomolecular Science and Technology, Université catholique
Degand, Hervé; Louvain Institute of Biomolecular Science and Technology, Université catholique
Morsomme, Pierre ; Louvain Institute of Biomolecular Science and Technology, Université catholique
Soumillion, Patrice ; Louvain Institute of Biomolecular Science and Technology, Université catholique
Delvigne, Frank ; Université de Liège - ULiège > Département GxABT > Microbial technologies ; Microbial Processes and Interactions, TERRA Research and Teaching Center
Hols, Pascal ; Louvain Institute of Biomolecular Science and Technology, Université catholique
Language :
English
Title :
Competence shut-off by intracellular pheromone degradation in salivarius streptococci.
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