Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution

Nature Microbiology volume 4, pages 97–111 (2019)Cite this article

Subjects

Abstract

Bacterial quorum-sensing autoinducers are small chemicals released to control microbial community behaviours. N-(3-oxo-dodecanoyl) homoserine lactone, the autoinducer of the Pseudomonas aeruginosa LasI–LasR circuitry, triggers significant cell death in lymphocytes. We found that this molecule is incorporated into the mammalian plasma membrane and induces dissolution of eukaryotic lipid domains. This event expels tumour necrosis factor receptor 1 into the disordered lipid phase for its spontaneous trimerization without its ligand and drives caspase 3–caspase 8-mediated apoptosis. In vivo, P. aeruginosa releases N-(3-oxo-dodecanoyl) homoserine lactone to suppress host immunity for its own better survival; conversely, blockage of caspases strongly reduces the severity of the infection. This work reveals an unknown communication method between microorganisms and the mammalian host and suggests interventions of bacterial infections by intercepting quorum-sensing signalling.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: 3oc induces TNFR1 pathway-mediated apoptosis.
Fig. 2: 3oc disrupts the structure of the plasma membrane.
Fig. 3: 3oc induces TNFR1 autotrimerization.
Fig. 4: 3oc alters the motion pattern of TNFR1 on the plasma membrane.
Fig. 5: 3oc-induced neutrophil apoptosis promotes P. aeruginosa infection.
Fig. 6: Proposed mechanism for the role of 3oc in Pseudomonas aeruginosa infection.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon request. Complete western blot images of all figures in the manuscript are provided as Supplementary Figures.

References

  1. Schuster, M., Sexton, D. J., Diggle, S. P. & Greenberg, E. P. Acyl-homoserine lactone quorum sensing: from evolution to application. Annu. Rev. Microbiol. 67, 43–63 (2013).

    Article  CAS  PubMed  Google Scholar 

  2. Smith, E. E. et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl Acad. Sci. USA 103, 8487–8492 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. McManus, A. T., Mason, A. D. Jr, McManus, W. F. & Pruitt, B. A. Jr. Twenty-five year review of Pseudomonas aeruginosa bacteremia in a burn center. Eur. J. Clin. Microbiol. 4, 219–223 (1985).

    Article  CAS  PubMed  Google Scholar 

  4. Pearson, J. P., Passador, L., Iglewski, B. H. & Greenberg, E. P. A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 92, 1490–1494 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Davies, D. G. et al. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280, 295–298 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Wagner, C. et al. The quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) enhances the host defence by activating human polymorphonuclear neutrophils (PMN). Anal. Bioanal. Chem. 387, 481–487 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Tateda, K. et al. The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils. Infect. Immun. 71, 5785–5793 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Skindersoe, M. E. et al. Pseudomonas aeruginosa quorum-sensing signal molecules interfere with dendritic cell-induced T-cell proliferation. FEMS Immunol. Med. Microbiol. 55, 335–345 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Glucksam-Galnoy, Y. et al. The bacterial quorum-sensing signal molecule N-3-oxo-dodecanoyl-l-homoserine lactone reciprocally modulates pro- and anti-inflammatory cytokines in activated macrophages. J. Immunol. 191, 337–344 (2013).

    Article  CAS  PubMed  Google Scholar 

  10. Smith, R. S., Harris, S. G., Phipps, R. & Iglewski, B. The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo. J. Bacteriol. 184, 1132–1139 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kravchenko, V. V. et al. Modulation of gene expression via disruption of NF-κB signaling by a bacterial small molecule. Science 321, 259–263 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Jacobi, C. A. et al. Effects of bacterial N-acyl homoserine lactones on human Jurkat T lymphocytes-OdDHL induces apoptosis via the mitochondrial pathway. Int. J. Med. Microbiol. 299, 509–519 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Kravchenko, V. V. et al. N-(3-oxo-acyl)homoserine lactones signal cell activation through a mechanism distinct from the canonical pathogen-associated molecular pattern recognition receptor pathways. J. Biol. Chem. 281, 28822–28830 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Davis, B. M., Jensen, R., Williams, P. & O’Shea, P. The interaction of N-acylhomoserine lactone quorum sensing signaling molecules with biological membranes: implications for inter-kingdom signaling. PLoS ONE 5, e13522 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Favre-Bonte, S., Chamot, E., Kohler, T., Romand, J. A. & van Delden, C. Autoinducer production and quorum-sensing dependent phenotypes of Pseudomonas aeruginosa vary according to isolation site during colonization of intubated patients. BMC Microbiol. 7, 33 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chhabra, S. R. et al. Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-l-homoserine lactone as immune modulators. J. Med. Chem. 46, 97–104 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Charlton, T. S. et al. A novel and sensitive method for the quantification of N-3-oxoacyl homoserine lactones using gas chromatography–mass spectrometry: application to a model bacterial biofilm. Environ. Microbiol. 2, 530–541 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Erickson, D. L. et al. Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect. Immun. 70, 1783–1790 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hu, X. Proteolytic signaling by TNFα: caspase activation and IκB degradation. Cytokine 21, 286–294 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Atkinson, S., Chang, C. Y., Sockett, R. E., Camara, M. & Williams, P. Quorum sensing in Yersinia enterocolitica controls swimming and swarming motility. J. Bacteriol. 188, 1451–1461 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Barnhart, B. C., Alappat, E. C. & Peter, M. E. The CD95 type I/type II model. Semin. Immunol. 15, 185–193 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Lavrik, I. N. & Krammer, P. H. Regulation of CD95/Fas signaling at the DISC. Cell Death Differ. 19, 36–41 (2012).

    Article  CAS  PubMed  Google Scholar 

  23. Watanabe, N. et al. Continuous internalization of tumor necrosis factor receptors in a human myosarcoma cell line. J. Biol. Chem. 263, 10262–10266 (1988).

    CAS  PubMed  Google Scholar 

  24. Shiner, E. K. et al. Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling. Cell. Microbiol. 8, 1601–1610 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Smith, R. S. et al. IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF-κB and activator protein-2. J. Immunol. 167, 366–374 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Jahoor, A. et al. Peroxisome proliferator-activated receptors mediate host cell proinflammatory responses to Pseudomonas aeruginosa autoinducer. J. Bacteriol. 190, 4408–4415 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Valentine, C. D., Anderson, M. O., Papa, F. R. & Haggie, P. M. X-box binding protein 1 (XBP1s) is a critical determinant of Pseudomonas aeruginosa homoserine lactone-mediated apoptosis. PLoS Pathog. 9, e1003576 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhu, J., Chai, Y., Zhong, Z., Li, S. & Winans, S. C. Agrobacterium bioassay strain for ultrasensitive detection of N-acylhomoserine lactone-type quorum-sensing molecules: detection of autoinducers in Mesorhizobium huakuii. Appl. Environ. Microbiol. 69, 6949–6953 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schauder, S. & Bassler, B. L. The languages of bacteria. Genes Dev. 15, 1468–1480 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Legler, D. F., Micheau, O., Doucey, M. A., Tschopp, J. & Bron, C. Recruitment of TNF receptor 1 to lipid rafts is essential for TNFα-mediated NF-κB activation. Immunity 18, 655–664 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Muppidi, J. R., Tschopp, J. & Siegel, R. M. Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction. Immunity 21, 461–465 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Lambert, W., Soderberg, C. A., Rutsdottir, G., Boelens, W. C. & Emanuelsson, C. Thiol-exchange in DTSSP crosslinked peptides is proportional to cysteine content and precisely controlled in crosslink detection by two-step LC–MALDI MSMS. Protein Sci. 20, 1682–1691 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ulbrich, M. H. & Isacoff, E. Y. Subunit counting in membrane-bound proteins. Nat. Methods 4, 319–321 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Connell, S. D., Heath, G., Olmsted, P. D. & Kisil, A. Critical point fluctuations in supported lipid membranes. Faraday Discuss. 161, 91–111; discussion 113–150 (2013).

    Article  CAS  PubMed  Google Scholar 

  35. Rinia, H. A. & de Kruijff, B. Imaging domains in model membranes with atomic force microscopy. FEBS Lett. 504, 194–199 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Simons, K. & Vaz, W. L. Model systems, lipid rafts, and cell membranes. Annu. Rev. Biophys. Biomol. Struct. 33, 269–295 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Yuan, C., Furlong, J., Burgos, P. & Johnston, L. J. The size of lipid rafts: an atomic force microscopy study of ganglioside GM1 domains in sphingomyelin/DOPC/cholesterol membranes. Biophys. J. 82, 2526–2535 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sengupta, P., Hammond, A., Holowka, D. & Baird, B. Structural determinants for partitioning of lipids and proteins between coexisting fluid phases in giant plasma membrane vesicles. Biochim. Biophys. Acta 1778, 20–32 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. Fujiwara, T. K. et al. Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane. Mol. Biol. Cell 27, 1101–1119 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kusumi, A. et al. Membrane mechanisms for signal transduction: the coupling of the meso-scale raft domains to membrane-skeleton-induced compartments and dynamic protein complexes. Semin. Cell Dev. Biol. 23, 126–144 (2012).

    Article  CAS  PubMed  Google Scholar 

  41. Kusumi, A., Tsunoyama, T. A., Hirosawa, K. M., Kasai, R. S. & Fujiwara, T. K. Tracking single molecules at work in living cells. Nat. Chem. Biol. 10, 524–532 (2014).

    Article  CAS  PubMed  Google Scholar 

  42. Suzuki, K. G. et al. Transient GPI-anchored protein homodimers are units for raft organization and function. Nat. Chem. Biol. 8, 774–783 (2012).

    Article  CAS  PubMed  Google Scholar 

  43. Moens, P. D., Digman, M. A. & Gratton, E. Modes of diffusion of cholera toxin bound to GM1 on live cell membrane by image mean square displacement analysis. Biophys. J. 108, 1448–1458 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Groot, R. D. & Warren, P. B. Dissipative particle dynamics: bridging the gap between atomistic and mesoscopic simulation. J. Chem. Phys. 107, 4423–4435 (1997).

    Article  CAS  Google Scholar 

  45. Williams, P. et al. Quorum sensing and the population-dependent control of virulence. Phil. Trans. R. Soc. Lond. B 355, 667–680 (2000).

    Article  CAS  Google Scholar 

  46. Davies, D. G. et al. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280, 295–298 (1998).

    Article  CAS  PubMed  Google Scholar 

  47. Schuster, M., Sexton, D. J., Diggle, S. P. & Greenberg, E. P. Acyl-homoserine lactone quorum sensing: from evolution to application. Annu. Rev. Microbiol. 67, 43–63 (2013).

    Article  CAS  PubMed  Google Scholar 

  48. Brumatti, G. et al. The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. Sci. Transl Med. 8, 339ra369 (2016).

    Article  Google Scholar 

  49. Barreyro, F. J. et al. The pan-caspase inhibitor emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver Int. 35, 953–966 (2015).

    Article  CAS  PubMed  Google Scholar 

  50. Xu, M. et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat. Med. 22, 1101–1107 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Teplitski, M., Mathesius, U. & Rumbaugh, K. P. Perception and degradation of N-acyl homoserine lactone quorum sensing signals by mammalian and plant cells. Chem. Rev. 111, 100–116 (2011).

    Article  CAS  PubMed  Google Scholar 

  52. Miyairi, S. et al. Immunization with 3-oxododecanoyl-l-homoserine lactone–protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection. J. Med. Microbiol. 55, 1381–1387 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Schwarzer, C. et al. Paraoxonase 2 serves a proapopotic function in mouse and human cells in response to the Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-homoserine lactone. J. Biol. Chem. 290, 7247–7258 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Horke, S. et al. Novel paraoxonase 2-dependent mechanism mediating the biological effects of the Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxo-dodecanoyl)-l-homoserine lactone. Infect. Immun. 83, 3369–3380 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Tao, S. et al. Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone. Sci. Rep. 6, 28778 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wagner, V. E., Bushnell, D., Passador, L., Brooks, A. I. & Iglewski, B. H. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J. Bacteriol. 185, 2080–2095 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Saenz, J. P. et al. Hopanoids as functional analogues of cholesterol in bacterial membranes. Proc. Natl Acad. Sci. USA 112, 11971–11976 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ritchie, K., Iino, R., Fujiwara, T., Murase, K. & Kusumi, A. The fence and picket structure of the plasma membrane of live cells as revealed by single molecule techniques (review). Mol. Membr. Biol. 20, 13–18 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Barnoud, J., Rossi, G., Marrink, S. J. & Monticelli, L. Hydrophobic compounds reshape membrane domains. PLoS Comput. Biol. 10, e1003873 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Legler, D. F., Doucey, M. A., Cerottini, J. C., Bron, C. & Luescher, I. F. Selective inhibition of CTL activation by a dipalmitoyl-phospholipid that prevents the recruitment of signaling molecules to lipid rafts. FASEB J. 15, 1601–1603 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Joelsson, A. C. & Zhu, J. LacZ-detection of acyl-homoserine lactone quorum-sensing signals. Curr. Protoc. Microbiol. 3, 1C.2.1–1C.2.9 (2006).

    Article  Google Scholar 

  62. Clayton, D. A. & Shadel, G. S. Isolation of mitochondria from tissue culture cells. Cold Spring Harb. Protoc. 2014, pdb.prot080002 (2014).

    Article  PubMed  Google Scholar 

  63. Kusumi, A., Sako, Y. & Yamamoto, M. Confined lateral diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium-induced differentiation in cultured epithelial cells. Biophys. J. 65, 2021–2040 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Facchini, M., De Fino, I., Riva, C. & Bragonzi, A. Long term chronic Pseudomonas aeruginosa airway infection in mice. J. Vis. Exp. 85, 51019 (2014).

    Google Scholar 

  65. Lukinskiene, L. et al. Antimicrobial activity of PLUNC protects against Pseudomonas aeruginosa infection. J. Immunol. 187, 382–390 (2011).

    Article  CAS  PubMed  Google Scholar 

  66. Sulahian, T. H., Imrich, A., Deloid, G., Winkler, A. R. & Kobzik, L. Signaling pathways required for macrophage scavenger receptor-mediated phagocytosis: analysis by scanning cytometry. Respir. Res. 9, 59 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  67. de Jong, A. et al. CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens. Nat. Immunol. 15, 177–185 (2014).

    Article  PubMed  Google Scholar 

  68. Tachi, M. & Iwamori, M. Mass spectrometric characterization of cholesterol esters and wax esters in epidermis of fetal, adult and keloidal human skin. Exp. Dermatol. 17, 318–323 (2008).

    Article  CAS  PubMed  Google Scholar 

  69. Owen, D. M., Rentero, C., Magenau, A., Abu-Siniyeh, A. & Gaus, K. Quantitative imaging of membrane lipid order in cells and organisms. Nat. Protoc. 7, 24–35 (2011).

    Article  PubMed  Google Scholar 

  70. Jin, L. et al. Characterization and application of a new optical probe for membrane lipid domains. Biophys. J. 90, 2563–2575 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kim, H. M. et al. A two-photon fluorescent probe for lipid raft imaging: C-laurdan. Chembiochem 8, 553–559 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Collins, M. D. & Gordon, S. E. Giant liposome preparation for imaging and patch-clamp electrophysiology. J. Vis. Exp. 76, 50227 (2013).

    Google Scholar 

  73. Pott, T., Bouvrais, H. & Meleard, P. Giant unilamellar vesicle formation under physiologically relevant conditions. Chem. Phys. Lipids 154, 115–119 (2008).

    Article  CAS  PubMed  Google Scholar 

  74. Klymchenko, A. S. & Kreder, R. Fluorescent probes for lipid rafts: from model membranes to living cells. Chem. Biol. 21, 97–113 (2014).

    Article  CAS  PubMed  Google Scholar 

  75. Groot, R. D. & Warren, P. B. Dissipative particle dynamics: bridging the gap between atomistic and mesoscopic simulation. J. Chem. Phys. 107, 4423–4435 (1997).

    Article  CAS  Google Scholar 

  76. Tieleman, D. P., Leontiadou, H., Mark, A. E. & Marrink, S. J. Simulation of pore formation in lipid bilayers by mechanical stress and electric fields. J. Am. Chem. Soc. 125, 6382–6383 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Chen, P. et al. Diffusion and directionality of charged nanoparticles on lipid bilayer membrane. ACS Nano 10, 11541–11547 (2016).

    Article  CAS  PubMed  Google Scholar 

  78. Vattulainen, I., Karttunen, M., Besold, G. & Polson, J. M. Integration schemes for dissipative particle dynamics simulations: from softly interacting systems towards hybrid models. J. Chem. Phys. 116, 3967–3979 (2002).

    Article  CAS  Google Scholar 

  79. Smith, K. A., Jasnow, D. & Balazs, A. C. Designing synthetic vesicles that engulf nanoscopic particles. J. Chem. Phys. 127, 084703 (2007).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank P. Greenberg of University of Washington for his expert advice and his gift of P. aeruginosa strains, J. Yuan of Institute of Chemistry of CAS for his assistance on single-molecule imaging data analysis, J. Harrison and H. Almblad for their expert advice on P. aeruginosa mutagenesis and L. Yu of Tsinghua University for DNA constructs. X.F. is supported by the National Natural Science Foundation of China (21735006 and 91413119). Y.S. is supported by the joint Peking-Tsinghua Center for Life Sciences, the National Natural Science Foundation of China General Program (31370878), and by grants from the US NIH (R01AI098995), the Natural Sciences and Engineering Research Council of Canada (RGPIN-355350/396037) and the Canadian Institutes for Health Research (MOP-119295).

Author information

Authors and Affiliations

  1. Institute for Immunology, Department of Basic Medical Sciences, Center for Life Sciences, Tsinghua University, Beijing, China

    Dingka Song, Junchen Meng, Hefei Ruan, Ning Kang, Ying Xu, Xiaobo Wang, Fei Shu, Libing Mu, Tengfei Li, Wenran Ren, Xin Lin, Tie Xia & Yan Shi

  2. Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China

    Jie Cheng & Junhong Lü

  3. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China

    Zheng Fan & Weihui Wu

  4. Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing, China

    Pengyu Chen & Li-Tang Yan

  5. Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute, University of Calgary, Calgary, Alberta, Canada

    Zhongyuan Tu & Yan Shi

  6. Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China

    Nan Li & Xiaohong Fang

  7. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Jun Zhu

  8. Department of Microbiology, Nanjing Agricultural University, Nanjing, China

    Jun Zhu

  9. Departments of Cell Biology and Anatomy, Snyder Institute, University of Calgary, Calgary, Alberta, Canada

    Matthias W. Amrein

Authors
  1. Dingka Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junchen Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zheng Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pengyu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hefei Ruan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhongyuan Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ning Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ying Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiaobo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Fei Shu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Libing Mu
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Tengfei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Wenran Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Xin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jun Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Xiaohong Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Matthias W. Amrein
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Weihui Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Li-Tang Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Junhong Lü
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Tie Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Yan Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.S. performed all of the experiments and data analyses unless otherwise specified with assistance from J.M., Z.T., Y.X., X.W., F.S., N.L., W.R. and L.M. N.K. and J.C. performed the AFM analysis. J.L., T.X. and M.W.A. proposed and supervised the AFM experiments. X.L. helped to design the TNFR1 signalling assays. X.F. helped to design the single-molecule imaging experiments. J.Z. helped to design the quorum-sensing mutant experiments. H.R. designed and performed the GUV experiments. T.L. performed the TLC analysis. Z.F. and W.W. designed and constructed the vector-based lasI overexpression version of ΔlasR P. aeruginosa. P.C. and L-T.Y. designed and performed the TNFR1 simulation work. T.X. designed and supervised all imaging work. Y.S. conceptualized the work and wrote the manuscript with assistance from D.S.

Corresponding author

Correspondence to Yan Shi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figures 1–6, uncropped gels, Supplementary Tables 1 and 2, Supplementary References, Supplementary Video legends.

Reporting Summary

Supplementary Video 1

Sample movie of TNFR1 multiple-step fluorescence quenching.

Supplementary Video 2

Sample movie of AFM scanning of lipid membrane treated with DMSO.

Supplementary Video 3

Sample movie of AFM scanning of lipid membrane treated with 3oc.

Supplementary Video 4

Sample movie of TNFR1 single-particle tracking treated with DMSO.

Supplementary Video 5

Sample movie of TNFR1 single-particle tracking treated with 3oc.

Supplementary Video 6

Coarse-grained model of TNFR1’s dynamics on plasma membrane.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, D., Meng, J., Cheng, J. et al. Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution. Nat Microbiol 4, 97–111 (2019). https://doi.org/10.1038/s41564-018-0290-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41564-018-0290-8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing