Social cheating in Pseudomonas aeruginosa quorum sensing

Abstract

In a process termed quorum sensing, bacteria use diffusible chemical signals to coordinate cell density-dependent gene expression. In the human pathogen Pseudomonas aeruginosa, quorum sensing controls hundreds of genes, many of which encode extracellular virulence factors. Quorum sensing is required for P. aeruginosa virulence in animal models. Curiously, quorum sensing-deficient variants, most of which carry a mutation in the gene encoding the central quorum sensing regulator lasR, are frequently isolated from acute and chronic infections. The mechanism for their emergence is not known. Here we provide experimental evidence suggesting that these lasR mutants are social cheaters that cease production of quorum-controlled factors and take advantage of their production by the group. We detected an emerging subpopulation of lasR mutants after Ϸ100 generations of in vitro evolution of the P. aeruginosa wild-type strain under culture conditions that require quorum sensing for growth. Under such conditions, quorum sensing appears to impose a metabolic burden on the proliferating bacterial cell, because quorum-controlled genes not normally induced until cessation of growth were highly expressed early in growth, and a defined lasR mutant showed a growth advantage when cocultured with the parent strain. The emergence of quorumsensing-deficient variants in certain environments is therefore an indicator of high quorum sensing activity of the bacterial population as a whole. It does not necessarily indicate that quorum sensing is insignificant, as has previously been suggested. Thus, novel antivirulence strategies aimed at disrupting bacterial communication may be particularly effective in such clinical settings.acyl-homoserine lactone ͉ bacterial communication ͉ evolution ͉ lasR ͉ virulence

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

“…This is precisely what was observed when WT P. aeruginosa (cooperators) was cocultured with lasR rhlR double mutant bacteria (cheaters) in QSrequiring media; overall, the growth of the culture was hampered compared to that of a pure WT culture (347). Similar results were observed with a single lasR mutant during coculture under conditions requiring QS for growth (348). However, private goods controlled by QS (for example, nucleoside hydrolase, which allows for growth of P. aeruginosa on adenosine) are found to limit the emergence of cheaters when resources attainable only by private goods are at sufficient levels in the environment (349).…”

Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis

“…Notably, mutations in the lasR gene involved in quorum sensing, a bacterial method of cellto-cell communication that is mediated by secretion of small molecules when the bacterial cells achieve high densities and that is needed for maximal formation of biofilms, were commonly found, suggesting this system might not be a major factor in the infected CF lung. However, a recent report [59] suggests that lasR mutants might be 'social cheaters' taking advantage of quorum sensing molecules made by a minority of strains within a genetically variant population, such as occurs in the CF lung, to maintain quorum-sensing-dependent virulence traits. Another common mutational event in chronically infecting P. aeruginosa strains occurs in negative regulators of multidrug efflux pumps such as mexZ, leading to the enhanced production of the pumps and the associated increase in antibiotic resistance that usually occurs during the course of CF lung disease [25], probably due to selection during antibiotic therapy.…”

“…Notably, mutations in the lasR gene involved in quorum sensing, a bacterial method of cellto-cell communication that is mediated by secretion of small molecules when the bacterial cells achieve high densities and that is needed for maximal formation of biofilms, were commonly found, suggesting this system might not be a major factor in the infected CF lung. However, a recent report [59] suggests that lasR mutants might be 'social cheaters' taking advantage of quorum sensing molecules made by a minority of strains within a genetically variant population, such as occurs in the CF lung, to maintain quorum-sensing- Some aspects of this high degree of genetic change in P. aeruginosa might be facilitated by the frequent emergence of mutator variants in the CF lung due to mutations in the methyldirected mismatch repair (MMR) system, with mutations in the mutS gene frequently observed [60]. These changes are often associated with increased antibiotic resistance.…”

Multiple antibiotic resistance index, fitness and virulence potential in respiratory Pseudomonas aeruginosa from Jamaica

“…In this regard, the development of 'hypermutable' strains is expected to improve the adaptability of the bacteria to the diverse microenvironments of the respiratory system (Hogardt & Heesemann, 2013). Furthermore, mixed populations of P. aeruginosa, including QS WT and lasR mutants, have demonstrated cooperative behaviour, where the QS mutants appear to exploit the functional QS systems of other members of the population (Diggle et al, 2007;Sandoz et al, 2007). In this way, bacteria that have reduced fitness (such as lasR mutants) might be able to persist and benefit from the activities of the QS-active members of the community.…”