Dynamics of natural competence in Streptococcus salivarius

Competence is one of the most successful survival strategies in bacteria. This powerful tactic synchronizes the production of antimicrobial compounds which eliminates competitors, providing genomic material availability for subsequent DNA uptake. Yet, competence regulation in streptococci is only partially understood. Particularly, the molecular mechanisms explaining how activation is restricted to a subpopulation (bimodality) and to a limited window of time (shut-off) are unknown. In this thesis, we aimed to decipher those complex mechanisms in the major commensal species Streptococcus salivarius. Combining molecular biology, biochemistry, microscopy and mathematical simulations, we unveil new regulatory pathways mastering ComRS, the major pheromone-pathway controlling competence in streptococci. In a first set of experiments, we show that the proportion of cells activating competence is directly linked to the concentration of the intracellular receptor ComR. We next demonstrate that this bimodal initiation requires a positive feedback loop on the pheromone comS, and identify the environmental sensor CovRS to control this process through comR regulation. We next describe a new degradation machinery of the pheromone controlled by competence activation, thereby ensuring ComRS shut-off. Finally, we uncover a link between bacterial cell-wall integrity and competence activation thanks to a genome-wide screen by CRISPR-interference. Altogether, those results help us understand how bacteria sense their environment and transmit it to complex regulatory pathways in order to produce collaborative and timed responses.
(SC - Sciences) -- UCL, 2022