Selection for increased quorum-sensing cooperation in Pseudomonas aeruginosa through the shut-down of a drug resistance pump

ISME J. 2018 Oct;12(10):2458-2469. doi: 10.1038/s41396-018-0205-y. Epub 2018 Jun 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Drug Resistance
  • Drug Resistance, Bacterial / physiology*
  • Gene Expression Regulation, Bacterial / genetics*
  • Gene Expression Regulation, Bacterial / physiology
  • Humans
  • Mutation
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / physiology*
  • Quorum Sensing / genetics
  • Quorum Sensing / physiology*
  • Virulence Factors

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Virulence Factors