Negative regulation of bacterial quorum sensing tunes public goods cooperation

Abstract

Bacterial quorum sensing (QS) often coordinates the expression of other, generally more costly public goods involved in virulence and nutrient acquisition. In many Proteobacteria, the basic QS circuitry consists of a synthase that produces a diffusible acyl-homoserine lactone and a cognate receptor that activates public goods expression. In some species, the circuitry also contains negative regulators that have the potential to modulate the timing and magnitude of activation. In this study, we experimentally investigated the contribution of this regulatory function to the evolutionary stability of public goods cooperation in the opportunistic pathogen Pseudomonas aeruginosa. We compared fitness and public goods expression rates of strains lacking either qteE or qscR, each encoding a distinct negative regulator, with those of the wild-type parent and a signalblind receptor mutant under defined growth conditions. We found that (1) qteE and qscR mutations behave virtually identically and have a stronger effect on the magnitude than on the timing of expression, (2) high expression in qteE and qscR mutants imposes a metabolic burden under nutrient conditions that advance induction and (3) high expression in qteE and qscR mutants increases population growth when QS is required, but also permits invasion by both wild-type and receptor mutant strains. Our data indicate that negative regulation of QS balances the costs and benefits of public goods by attenuating expression after transition to the induced state. As the cells cannot accurately assess the amount of cooperation needed, such bet-hedging would be advantageous in changing parasitic and nonparasitic environments.

Affecting Pseudomonas aeruginosa Phenotypic Plasticity by Quorum Sensing Dysregulation Hampers Pathogenicity in Murine Chronic Lung Infection

“…Overall, the above results are in agreement with previous studies showing that the lasI and lasB promoters are prematurely activated in the qteE mutant with respect to the wild type [17], [20], and that QteE overexpression causes repression of elastase and pyocyanin production in P. aeruginosa [20], [22]. Notably, our results demonstrate that in the qteE mutant the production of 3OC 12 -HSL and of main QS-controlled virulence factors is anticipated, and that these exo-products accumulate along growth at higher levels with respect to the wild type strain, supporting the hypothesis that qteE may play a role in P. aeruginosa pathogenesis.…”

“…Overall, this fine-tuning is believed to increase P. aeruginosa phenotypic plasticity and population fitness, ultimately facilitating colonization of challenging environments such as higher organisms' tissues [3], [14]–[17].…”

Core Principles of Bacterial Autoinducer Systems

“…Negative feedback loops introduced into the molecular architecture of AI production and/or sensing are often employed. For example, in P. aeruginosa, AI expression is repressed by the negative regulator RsaL (99, 100), while receptor activity is inhibited by the antiactivators QteE and QscR (101)(102)(103). AI induces the transcription of RsaL and QteE (76) and activates QscR as a ligand (104).…”

Cooperation in Microbial Populations: Theory and Experimental Model Systems

“…Signaling via autoinducers is known to be involved in the regulation of various pulic goods, including different types of pyoverdines. Such feedbacks can strongly affect the costs and beneficial aspects of public goods synthesis [141,124,310].…”