Selection for increased quorum-sensing cooperation in Pseudomonas aeruginosa through the shut-down of a drug resistance pump.
Ron D OshriKeren S ZrihenItzhak ShnerShira Omer BendoriAvigdor EldarPublished in: The ISME journal (2018)
The opportunistic pathogen Pseudomonas aeruginosa employs a hierarchical quorum-sensing network to regulate virulence factor production that cooperatively benefit the population at a cost to the individual. It has been argued that the evolution of a cooperative mutant in a quorum sensing-suppressed population would be hampered through its exploitation by neighboring non-mutant cells. It remains unclear whether mechanisms which overcome this exploitation exist. Here we investigate the regain of quorum-sensing cooperation by evolving a mutant of the lasR master quorum-sensing regulator. The mutant regained partial cooperative growth through null mutations in mexT, which codes for an activator of the MexEF-OprN multidrug-resistant pump. We find that these mutations enhance cooperative growth in both the lasR mutant and wild-type backgrounds through the activation of the RhlIR system. We show that the regain of cooperation in mexT mutants is mediated by the reduction in MexEF-OprN activity, whereas an additional source of private benefit is mostly mexEF-oprN-independent. Finally, we show that addition of antibiotics for which resistance is mediated by MexEF-OprN prevents the selection of increased cooperation at sub-MIC concentrations. MexT, therefore, not only links private and public goods, but also exposes conflicts between selection for antibiotic resistance and enhanced cooperation.
Keyphrases
- wild type
- pseudomonas aeruginosa
- multidrug resistant
- cystic fibrosis
- healthcare
- biofilm formation
- acinetobacter baumannii
- escherichia coli
- induced apoptosis
- health insurance
- staphylococcus aureus
- mental health
- cell cycle arrest
- transcription factor
- gram negative
- cell proliferation
- cell death
- bariatric surgery
- weight loss
- electronic health record
- signaling pathway
- nuclear factor