The CovRS Environmental Sensor Directly Controls the ComRS Signaling System To Orchestrate Competence Bimodality in Salivarius Streptococci

Abstract

Combining production of antibacterial compounds and uptake of DNA material released by dead cells, competence is one of the most efficient survival strategies in streptococci. Yet, this powerful tactic is energy consuming and reprograms the metabolism to such an extent that cell proliferation is transiently impaired.

Competence shut-off by intracellular pheromone degradation in salivarius streptococci

“…Indeed, we modeled a ComS/XIP degradation machinery quickly saturated ( Fig 1A and 1B [4 th panel]), which avoids spontaneous competence activation but allows high ComS production once overwhelmed. This resulted in a theoretical maximum free XIP concentration of 6 nM produced during competence ( Fig 1C ), which largely exceeds the experimentally determined sXIP threshold concentration (0.8 nM) required for activation [ 24 ]. Moreover, the introduction of the deg player generated a system that is only reactive at high ComR levels as previously shown with ComR-overproduction in single-cell experiments [ 24 ] ( S1 Fig ).…”

“…salivarius HSISS4 [ 37 ] have highlighted the central role of ComR abundance in competence activation [ 7 , 36 ]. Strikingly, while pheromone overexpression could not trigger comX transcriptional activation, synthetic pheromone (sXIP) addition generated a strong and unimodal response in the population [ 24 ]. To puzzle out this intriguing observation, we investigated the ComRS regulatory cascade by designing a deterministic model based on previous in silico modeling of S .…”

“…We introduced this unknown inhibitor in our model (named deg ), adjusted the free parameters, and compared the evolution of the cellular concentration of ComR, ComX and ComS with or without the deg variable ( Fig 1A and 1B ). In both cases, we simulated the ComR overproduction to high levels to trigger competence (up to 7,000 molecules per cell, according to a western-blot semi quantification previously performed [ 24 ]). As expected, free ComR intracellular concentration increases until a sharp drop corresponding to its conversion into the ComR · XIP complex ( Fig 1B , 1 st panel).…”

“…Dotted line denotes the minimum sXIP extracellular concentration experimentally determined to trigger competence in S . salivarius [ 24 ]. (D) ComS degradation rate over time computed for the model including the deg variable in two types of competence inducing processes.…”

“…To curtail this dramatic impact on the survival chance of the population, streptococci exploit complex regulatory networks to restrict competence activation to a subpopulation. This tactic known as bimodality or excitability (since transitory) allows only a subset of the community to play the dangerous but yet promising game of competence [ 5 , 24 ]. An auxiliary strategy aims to narrow the activation time window of this peculiar physiological state to restore routine cell-cycle once DNA has been internalized and integrated.…”