Pseudomonas aeruginosaisolates defective in function of the LasR quorum sensing regulator are frequent in diverse environmental niches

Abstract

The saprophyte Pseudomonas aeruginosa is a versatile opportunistic pathogen causing infections in immunocompromised individuals. To facilitate its adaptation to a large variety of niches, this bacterium exploits population density-dependant gene regulation systems called quorum sensing. In P. aeruginosa, three distinct but interrelated quorum sensing systems (las, rhl and pqs) regulate the production of many survival and virulence functions. In prototypical strains, the las system, through its transcriptional regulator LasR, is important for the full activation of the rhl and pqs systems. Still, LasR-deficient isolates have been reported, mostly sampled from the lungs of people with cystic fibrosis, where they are considered selected by the chronic infection environment. In this study, we show that a defect in LasR activity appears to be an actually widespread mechanism of adaptation in this bacterium. Indeed, we found abundant LasR-defective isolates sampled from hydrocarbon-contaminated soils, hospital sink drains, and meat/fish market environments, using an approach based on phenotypic profiling, supported by gene sequencing. Interestingly, several LasR-defective isolates maintain an active rhl system or are deficient in pqs system signaling. The high prevalence of a LasR-defective phenotype among environmental P. aeruginosa isolates questions the role of quorum sensing in niche adaptation.

Evolution of the quorum sensing systems in Pseudomonas aeruginosa can involve both loss of regulon function and network modulation

“…As an important human pathogen, the evolution of Pseudomonas aeruginosa populations has been studied in a myriad of context, with extensive genetic adaptation being repeatedly observed in diverging environments such as human cystic fibrosis (CF) lungs, animal infection models, as well as in the natural environments and in vitro experimental evolutions (Rumbaugh et al, 2009;Jansen et al, 2015;Feltner et al, 2016;Granato et al, 2018;Groleau et al, 2021;Scribner et al, 2021;Smalley et al, 2022). The quorum sensing (QS) regulon, a global three-unit regulatory system that controls the expression of up to 10% of the genes in P. aeruginosa, many of which include virulence factors, is often among the most mutated pathways.…”

“…P. aeruginosa isolates from chronically infected CF patient lungs frequently contain mutations in the master transcriptional regulator, LasR, thereby influencing the activity of all three QS systems (Feltner et al, 2016;Chen et al, 2019). While initially interpreted as a specific adaptation to the CF lung environment, it has become clear that lasR mutants are also selected for under many other conditions, including chronic wounds (Vanderwoude et al, 2020), corneal infections (Preston et al, 1997;Hammond et al, 2016), ventilator-associated pneumonia (Köhler, Buckling and Van Delden, 2009), infections in Caenorhabditis elegans (Jansen et al, 2015;Granato et al, 2018), as well as in the absence of a host such as in natural environments (Groleau et al, 2021) and in experimental evolutions (Wilder, Diggle and Schuster, 2011;Kostylev et al, 2019;Scribner et al, 2021;Smalley et al, 2022). Why then, are lasR mutants consistently favored across these difference environments?…”

Community composition shapes microbial-specific phenotypes in a cystic fibrosis polymicrobial model system

“…Based on our observations (Fig. 3) and given that loss of LasR function often results in overproduction of phenazines in various contexts (53,58,(66)(67)(68), we hypothesized that these molecules might be overproduced in the mixed community thereby conferring tolerance to the ΔlasR mutant.…”

“…P. aeruginosa undergoes genetic adaptation in the airway of pwCF (50) and loss-of-function mutations in the gene coding for the key intercellular communication regulator, LasR (51), are frequently observed in the airway of pwCF and other environments (52)(53)(54)(55)(56). Strains lacking LasR function have also been associated with worsened lung function (54), in vitro growth advantage in low oxygen conditions (57), increased production of virulence factors through intraspecies interactions (58) and greater tolerance to front-line CF drugs (59).…”

Study of Pseudomonas aeruginosa PPF-1 biofilm formation using microfluidics: effect of magnesium on biofilm detachment in engineered conduits

“…12 PPF-1 also contains a lasR gene alteration, 11 as observed in other P. aeruginosa known to proliferate in engineered and natural water systems such as swimming pools, rivers and hydrocarbon-contaminated soils, hospital sink drains, and meat/fish market environments. [13][14][15] The PPF-1 strain is an important producer of biofilms, 9 and consequently, studying biofilm formation by PPF-1 as a model strain is of interest. 10 Biofilms are surface-attached structures made of cells embedded in a self-produced extracellular polymeric matrix.…”