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

Oshri, Ron D, Zrihen, Keren S, Shner, Itzhak, Omer Bendori, Shira, Eldar, Avigdor·2018·The ISME Journal
DOI 10.1038/s41396-018-0205-y
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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.

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Research works printed but not linked: 64

  1. Xavier, 2007, Cooperation and conflict in microbial biofilms, Proc Natl Acad Sci, 104, 876, 10.1073/pnas.0607651104 · DOI · Paper page
  2. West, 2007, The social lives of microbes, Annu Rev Ecol Evol Syst, 38, 53, 10.1146/annurev.ecolsys.38.091206.095740 · DOI · Paper page
  3. Waters, 2005, Quorum sensing: cell-to-cell communication in bacteria, Annu Rev Cell Dev Biol, 21, 319, 10.1146/annurev.cellbio.21.012704.131001 · DOI · Paper page
  4. Schuster, 2013, Acyl-homoserine lactone quorum sensing: from evolution to application, Annu Rev Microbiol, 67, 43, 10.1146/annurev-micro-092412-155635 · DOI · Paper page
  5. Hense, 2007, Does efficiency sensing unify diffusion and quorum sensing?, Nat Rev Micro, 5, 230, 10.1038/nrmicro1600 · DOI · Paper page
  6. Darch, 2012, Density-dependent fitness benefits in quorum-sensing bacterial populations, Proc Natl Acad Sci, 109, 8259, 10.1073/pnas.1118131109 · DOI · Paper page
  7. Pai, 2012, Optimality and robustness in quorum sensing (QS)-mediated regulation of a costly public good enzyme, Proc Natl Acad Sci, 109, 19810, 10.1073/pnas.1211072109 · DOI
  8. Lee, 2015, The hierarchy quorum sensing network in Pseudomonas aeruginosa, Protein Cell, 6, 26, 10.1007/s13238-014-0100-x · DOI · Paper page
  9. Diggle, 2003, The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR, Mol Microbiol, 50, 29, 10.1046/j.1365-2958.2003.03672.x · DOI · Paper page
  10. Pesci, 1997, Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa, J Bacteriol, 179, 3127, 10.1128/jb.179.10.3127-3132.1997 · DOI · Paper page
  11. Schuster, 2006, A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa, Int J Med Microbiol, 296, 73, 10.1016/j.ijmm.2006.01.036 · DOI · Paper page
  12. McKnight, 2000, The Pseudomonas quinolone signal regulates rhl quorum sensing in Pseudomonas aeruginosa, J Bacteriol, 182, 2702, 10.1128/JB.182.10.2702-2708.2000 · DOI · Paper page
  13. Pearson, 1997, Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes, J Bacteriol, 179, 5756, 10.1128/jb.179.18.5756-5767.1997 · DOI · Paper page
  14. Schuster, 2003, Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis, J Bacteriol, 185, 2066, 10.1128/JB.185.7.2066-2079.2003 · DOI · Paper page
  15. Diggle, 2007, Cooperation and conflict in quorum-sensing bacterial populations, Nature, 450, 411, 10.1038/nature06279 · DOI · Paper page
  16. Pollitt, 2014, Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus, Infect Immun, 82, 1045, 10.1128/IAI.01216-13 · DOI
  17. Sandoz, 2007, Social cheating in Pseudomonas aeruginosa quorum sensing, Proc Natl Acad Sci, 104, 15876, 10.1073/pnas.0705653104 · DOI · Paper page
  18. Dandekar, 2012, Bacterial quorum sensing and metabolic incentives to cooperate, Science, 338, 264, 10.1126/science.1227289 · DOI · Paper page
  19. Feltner, 2016, LasR variant cystic fibrosis isolates reveal an adaptable quorum-sensing hierarchy in Pseudomonas aeruginosa, mBio, 7, e01513, 10.1128/mBio.01513-16 · DOI · Paper page
  20. Rumbaugh, 2009, Quorum sensing and the social evolution of bacterial virulence, Curr Biol, 19, 341, 10.1016/j.cub.2009.01.050 · DOI · Paper page
  21. Köhler, 2009, Cooperation and virulence of clinical Pseudomonas aeruginosa populations, Proc Natl Acad Sci, 106, 6339, 10.1073/pnas.0811741106 · DOI · Paper page
  22. Foster, 2006, The Phoenix effect, Nature, 441, 18, 10.1038/441291a · doi:10.1038/441291a
  23. Fiegna, 2006, Evolution of an obligate social cheater to a superior cooperator, Nature, 441, 310, 10.1038/nature04677 · DOI · Paper page
  24. Gore, 2009, Snowdrift game dynamics and facultative cheating in yeast, Nature, 459, 253, 10.1038/nature07921 · DOI · Paper page
  25. Granato, 2017, The path to re-evolve cooperation is constrained in Pseudomonas aeruginosa, BMC Evol Biol, 17, 214, 10.1186/s12862-017-1060-6 · DOI
  26. Defoirdt, 2010, Can bacteria evolve resistance to quorum sensing disruption?, PLoS Pathog, 6, e1000989, 10.1371/journal.ppat.1000989 · DOI · Paper page
  27. Allen, 2014, Targeting virulence: can we make evolution-proof drugs?, Nat Rev Microbiol, 12, 300, 10.1038/nrmicro3232 · DOI · Paper page
  28. Mellbye, 2011, The sociomicrobiology of antivirulence drug resistance: a proof of concept, mBio, 2, e00131, 10.1128/mBio.00131-11 · DOI · Paper page
  29. Gerdt, 2014, Competition Studies Confirm Two Major Barriers That Can Preclude the Spread of Resistance to Quorum-Sensing Inhibitors in Bacteria, ACS Chemical Biology, 9, 2291, 10.1021/cb5004288 · DOI
  30. Köhler, 2010, Quorum sensing inhibition selects for virulence and cooperation in Pseudomonas aeruginosa, PLoS Pathog, 6, e1000883, 10.1371/journal.ppat.1000883 · DOI · Paper page
  31. Maeda, 2012, Quorum quenching quandary: resistance to antivirulence compounds, ISME J, 6, 493, 10.1038/ismej.2011.122 · DOI · Paper page
  32. Steindler, 2009, LasI/R and RhlI/R quorum sensing in a strain of Pseudomonas aeruginosa beneficial to plants, Appl Environ Microbiol, 75, 5131, 10.1128/AEM.02914-08 · DOI
  33. Cabeen, 2014, Stationary phase-specific virulence factor overproduction by a lasR mutant of Pseudomonas aeruginosa, PLoS ONE, 9, e88743, 10.1371/journal.pone.0088743 · doi:10.1371/journal.pone.0088743
  34. Medina, 2003, Transcriptional regulation of Pseudomonas aeruginosa rhlR, encoding a quorum-sensing regulatory protein, Microbiology, 149, 3073, 10.1099/mic.0.26282-0 · doi:10.1099/mic.0.26282-0
  35. Van Delden, 1998, Starvation selection restores elastase and rhamnolipid production in a Pseudomonas aeruginosa quorum-sensing mutant, Infect Immun, 66, 4499, 10.1128/IAI.66.9.4499-4502.1998 · DOI
  36. Schweizer, 1992, Alielic exchange in Pseudomonas aeruginosa using novel ColE1-type vectors and a family of cassettes containing a portable oriT and the counter-selectable Bacillus subtilis sacB marker, Mol Microbiol, 6, 1195, 10.1111/j.1365-2958.1992.tb01558.x · DOI · Paper page
  37. Miller, 2000, Improved gfp and inaZ broad-host-range promoter-probe vectors, Mol Plant Microbe Interact, 13, 1243, 10.1094/MPMI.2000.13.11.1243 · DOI · Paper page
  38. Davies, 1998, The involvement of cell-to-cell signals in the development of a bacterial biofilm, Science, 280, 295, 10.1126/science.280.5361.295 · DOI · Paper page
  39. Xavier, 2011, A molecular mechanism that stabilizes cooperative secretions in Pseudomonas aeruginosa, Mol Microbiol, 79, 166, 10.1111/j.1365-2958.2010.07436.x · DOI · Paper page
  40. Hickman, 2008, Identification of FleQ from Pseudomonas aeruginosa as ac-di-GMP-responsive transcription factor, Mol Microbiol, 69, 376, 10.1111/j.1365-2958.2008.06281.x · DOI · Paper page
  41. Kiely, 2008, Genetic analysis of genes involved in dipeptide metabolism and cytotoxicity in Pseudomonas aeruginosa PAO1, Microbiology, 154, 2209, 10.1099/mic.0.2007/015032-0 · doi:10.1099/mic.0.2007/015032-0
  42. Asfahl, 2015, Non-social adaptation defers a tragedy of the commons in Pseudomonas aeruginosa quorum sensing, ISME J, 9, 1734, 10.1038/ismej.2014.259 · doi:10.1038/ismej.2014.259
  43. Tian, 2009, Transcriptome profiling defines a novel regulon modulated by the LysR-type transcriptional regulator MexT in Pseudomonas aeruginosa, Nucleic Acids Res, 37, 7546, 10.1093/nar/gkp828 · DOI
  44. Maseda, 2000, Variation of the mexT gene, a regulator of the MexEF-oprN efflux pump expression in wild-type strains of Pseudomonas aeruginosa, FEMS Microbiol Lett, 192, 107, 10.1111/j.1574-6968.2000.tb09367.x · DOI
  45. Maseda, 2000, Assignment of the substrate-selective subunits of the MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa, Antimicrob Agents Chemother, 44, 658, 10.1128/AAC.44.3.658-664.2000 · DOI
  46. Luong, 2014, Emergence of the P2 phenotype in pseudomonas aeruginosa PAO1 strains involves various mutations in mexT or mexF, J Bacteriol, 196, 504, 10.1128/JB.01050-13 · doi:10.1128/jb.01050-13
  47. Köhler, 2001, Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa, J Bacteriol, 183, 5213, 10.1128/JB.183.18.5213-5222.2001 · DOI · Paper page
  48. Maseda, 2004, Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa, Antimicrob Agents Chemother, 48, 1320, 10.1128/AAC.48.4.1320-1328.2004 · DOI · Paper page
  49. Lamarche, 2011, MexEF-OprN efflux pump exports the Pseudomonas quinolone signal (PQS) precursor HHQ (4-hydroxy-2-heptylquinoline), PLoS ONE, 6, e24310, 10.1371/journal.pone.0024310 · DOI
  50. Wade, 2005, Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa, J Bacteriol, 187, 4372, 10.1128/JB.187.13.4372-4380.2005 · DOI · Paper page
  51. McGrath, 2004, Dueling quorum sensing systems in Pseudomonas aeruginosa control the production of the Pseudomonas quinolone signal (PQS), FEMS Microbiol Lett, 230, 27, 10.1016/S0378-1097(03)00849-8 · DOI · Paper page
  52. Déziel, 2004, Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication, Proc Natl Acad Sci USA, 101, 1339, 10.1073/pnas.0307694100 · DOI · Paper page
  53. Tian, 2009, MexT modulates virulence determinants in Pseudomonas aeruginosa independent of the MexEF-OprN efflux pump, Microb Pathog, 47, 237, 10.1016/j.micpath.2009.08.003 · doi:10.1016/j.micpath.2009.08.003
  54. Olivas, 2012, Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak, PloS ONE, 7, e44326, 10.1371/journal.pone.0044326 · DOI · Paper page
  55. Köhler, 1997, Characterization of MexE–MexF–OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa, Mol Microbiol, 23, 345, 10.1046/j.1365-2958.1997.2281594.x · DOI · Paper page
  56. Olivares, 2014, Metabolic compensation of fitness costs associated with overexpression of the multidrug efflux pump MexEF-OprN in Pseudomonas aeruginosa, Antimicrob Agents Chemother, 58, 3904, 10.1128/AAC.00121-14 · DOI
  57. Wang, 2015, Quorum sensing and policing of Pseudomonas aeruginosasocial cheaters, Proceedings of the National Academy of Sciences, 112, 2187, 10.1073/pnas.1500704112 · DOI · Paper page
  58. Foster, 2004, Pleiotropy as a mechanism to stabilize cooperation, Nature, 431, 693, 10.1038/nature02894 · DOI · Paper page
  59. Travisano, 2004, Strategies of microbial cheater control, Trends Microbiol, 12, 72, 10.1016/j.tim.2003.12.009 · DOI · Paper page
  60. Mitri, 2016, Pleiotropy and the low cost of individual traits promote cooperation, Evolution, 70, 488, 10.1111/evo.12851 · DOI
  61. Minagawa, 2012, RND type efflux pump system MexAB-OprM of pseudomonas aeruginosa selects bacterial languages, 3-oxo-acyl-homoserine lactones, for cell-to-cell communication, BMC Microbiol, 12, 70, 10.1186/1471-2180-12-70 · doi:10.1186/1471-2180-12-70
  62. Pearson, 1999, Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals, J Bacteriol, 181, 1203, 10.1128/JB.181.4.1203-1210.1999 · DOI · Paper page
  63. Evans, 1998, Influence of the MexAB-OprM multidrug efflux system on quorum sensing in Pseudomonas aeruginosa, J Bacteriol, 180, 5443, 10.1128/JB.180.20.5443-5447.1998 · DOI · Paper page
  64. Chan, 2005, The Burkholderia pseudomallei BpeAB-OprB efflux pump: expression and impact on quorum sensing and virulence, J Bacteriol, 187, 4707, 10.1128/JB.187.14.4707-4719.2005 · DOI

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Metadata

Authors
Oshri, R. D., Zrihen, K. S., Shner, I., Omer Bendori, S., & Eldar, A.
Venue
The ISME Journal
Publisher
Oxford University Press (OUP)
Published
2018-06-20
Volume
12
Issue
10
Pages
2458-2469
ISSN
  • 1751-7362
  • 1751-7370
DOI
10.1038/s41396-018-0205-y
Cited by
82
References
1
Language
en
Licence
Funders
  • Israel Science Foundation (418/15)
  • EC | European Research Council (281301)
  • Israel Science Foundation (ISF) (418/15)
  • EC | European Research Council (ERC) (281301)

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Oshri, R. D., Zrihen, K. S., Shner, I., Omer Bendori, S., & Eldar, A. (2018). Selection for increased quorum-sensing cooperation in Pseudomonas aeruginosa through the shut-down of a drug resistance pump. The ISME Journal. https://doi.org/10.1038/s41396-018-0205-y

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