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Competence shut-off by intracellular pheromone degradation in salivarius streptococci

Adrien Knoops, Laura Ledesma-Garcia, Alexandra Waegemans, Morgane Lamontagne,Baptiste Decat,Herve Degand,Pierre Morsomme, Patrice Soumillion, Frank Delvigne, Pascal Hols

PLoS genetics(2022)

Cited 2|Views23
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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. Author summaryThe human oral cavity is one of the most challenging ecological niches for bacteria. In this ecosystem, hundreds of species compete for food and survival in a physicochemical fluctuating environment. To outcompete, Streptococcus salivarius has developed a particular physiological state called competence during which antibacterial compounds are produced together with the uptake of external DNA that can be integrated in its own genome. Although this strategy is of main importance for evolution and adaptation, its short-term cost in terms of energy and metabolism reprogramming are important. To restrain competence activation to a sharp window of time, bacteria use a process known as shut-off. Although described in some species, this process is still mostly unknown in streptococci. In this work, we used predictive mathematical simulations to infer the role of a pheromone-degradation machinery involved in the exit from competence. We confirmed experimentally this mechanism by identifying PepF as a competence-induced oligoendopeptidase with a specific activity towards the XIP pheromone. Importantly, we show that this peptidase is not only shutting down competence but also preventing its development under inappropriate conditions.
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Key words
intracellular pheromone degradation,shut-off
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