Social cheating in Pseudomonas aeruginosa quorum sensing.
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 approximately 100 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 quorum-sensing-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.
Sandoz
Kelsi M
KM
Department of Biomedical Sciences and Microbiology, Oregon State University, Corvallis, OR 97331, USA.
Mitzimberg
Shelby M
SM
Schuster
Martin
M
D002450:Cell Communication / Q000502:physiology; D002455:Cell Division; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology*; D014774:Virulence