Skip to main content
SpringerLink
Log in

Convergence of hormones and autoinducers at the host/pathogen interface

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Most living organisms possess sophisticated cell-signaling networks in which lipid-based signals modulate biological effects such as cell differentiation, reproduction and immune responses. Acyl homoserine lactone (AHL) autoinducers are fatty acid-based signaling molecules synthesized by several Gram-negative bacteria that are used to coordinate gene expression in a process termed “quorum sensing” (QS). Recent evidence shows that autoinducers not only control gene expression in bacterial cells, but also alter gene expression in mammalian cells. These alterations include modulation of proinflammatory cytokines and induction of apoptosis. Some of these responses may have deleterious effects on the host’s immune response, thereby leading to increased bacterial pathogenesis. Prokaryotes and eukaryotes have cohabited for approximately two billion years, during which time they have been exposed to each others’ soluble signaling molecules. We postulate that organisms from the different kingdoms of nature have acquired mechanisms to sense and respond to each others signaling molecules, and we have named this process interkingdom signaling. We further propose that autoinducers, which exhibit structural and functional similarities to mammalian lipid-based hormones, are excellent candidates for mediating this interkingdom communication. Here we will compare and contrast bacterial QS systems with eukaryotic endocrine systems, and discuss the mechanisms by which autoinducers may exploit mammalian signal transduction pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3A, B

Similar content being viewed by others

References

  1. Fox JE (2004) Chemical communication threatened by endocrine-disrupting chemicals. Environ Health Perspect 112:648–53

    Article  CAS  Google Scholar 

  2. Lyon GJ, Novick RP (2004) Peptide signaling in Staphylococcus aureus and other Gram-positive bacteria. Peptides 25:1389–403

    Article  CAS  Google Scholar 

  3. Sturme MH et al. (2002) Cell-to-cell communication by autoinducing peptides in Gram-positive bacteria. Antonie Van Leeuwenhoek 81:233–243

    Article  CAS  Google Scholar 

  4. Miller MB, Bassler BL (2001) Quorum sensing in bacteria. Annu Rev Microbiol 55:165–199

    Article  CAS  Google Scholar 

  5. Kleerebezem M, Quadri LE, Kuipers OP, de Vos WM (1997) Quorum sensing by peptide pheromones and two-component signal-transduction systems in Gram-positive bacteria. Mol Microbiol 24:895–904

    Article  CAS  Google Scholar 

  6. Downward J (2001) The ins and outs of signalling. Nature 411:759–762

    Article  CAS  Google Scholar 

  7. Furnes H, Banerjee NR, Muehlenbachs K, Staudigel H, de Wit M (2004) Early life recorded in archean pillow lavas. Science 304:578–581

    Article  CAS  Google Scholar 

  8. Fraser-Liggett CM (2005) Insights on biology and evolution from microbial genome sequencing. Genome Res 15:1603–1610

    Article  CAS  Google Scholar 

  9. Fuqua C, Winans SC, Greenberg EP (1996) Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators. Annu Rev Microbiol 50:727–751

    Article  CAS  Google Scholar 

  10. Hardman AM, Stewart GS, Williams P (1998) Quorum sensing and the cell–cell communication dependent regulation of gene expression in pathogenic and non-pathogenic bacteria. Antonie Van Leeuwenhoek 74:199–210

    Article  CAS  Google Scholar 

  11. Waters CM, Bassler BL (2005) Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol

  12. Reading NC, Sperandio V (2006) Quorum sensing: the many languages of bacteria. FEMS Microbiol Lett 254:1–11

    Article  CAS  Google Scholar 

  13. Venturi V (2006) Regulation of quorum sensing in Pseudomonas. FEMS Microbiol Rev 30:274–291

    Article  CAS  Google Scholar 

  14. Diekman MA, Green ML (1992) Mycotoxins and reproduction in domestic livestock. J Anim Sci 70:1615–1627

    CAS  Google Scholar 

  15. Gajecki M (2002) Zearalenone—undesirable substances in feed. Pol J Vet Sci 5:117–122

    CAS  Google Scholar 

  16. Hornby JM et al. (2001) Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl Environ Microbiol 67:2982–2992

    Article  CAS  Google Scholar 

  17. Ramage G, Saville SP, Wickes BL, Lopez-Ribot JL (2002) Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Appl Environ Microbiol 68:5459–5463

    Article  CAS  Google Scholar 

  18. Chen H, Fujita M, Feng Q, Clardy J, Fink GR (2004) Tyrosol is a quorum-sensing molecule in Candida albicans. Proc Natl Acad Sci USA 101:5048–5052

    Article  CAS  Google Scholar 

  19. Duncan RE, Archer MC (2006) Farnesol induces thyroid hormone receptor (THR) beta1 but inhibits THR-mediated signaling in MCF-7 human breast cancer cells. Biochem Biophys Res Commun

  20. Wang Z, Chen HT, Roa W, Finlay W (2003) Farnesol for aerosol inhalation: nebulization and activity against human lung cancer cells. J Pharm Pharm Sci 6:95–100

    Google Scholar 

  21. Forman BM et al. (1995) Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81:687–693

    Article  CAS  Google Scholar 

  22. Takahashi N et al. (2002) Dual action of isoprenols from herbal medicines on both PPAR-gamma and PPAR-alpha in 3T3-L1 adipocytes and HepG2 hepatocytes. FEBS Lett 514:315–322

    Article  CAS  Google Scholar 

  23. Gray WM (2004) Hormonal regulation of plant growth and development. PLoS Biol 2:E311

    Article  CAS  Google Scholar 

  24. Turlings TC et al. (1995) How caterpillar-damaged plants protect themselves by attracting parasitic wasps. Proc Natl Acad Sci USA 92:4169–4174

    Article  CAS  Google Scholar 

  25. Vet LE (1999) Evolutionary aspects of plant-carnivore interactions. Novartis Found Symp 223:3–13, discussion 13–20, 39–42

    Article  CAS  Google Scholar 

  26. Wynne-Edwards KE (2001) Evolutionary biology of plant defenses against herbivory and their predictive implications for endocrine disruptor susceptibility in vertebrates. Environ Health Perspect 109:443–448

    Article  CAS  Google Scholar 

  27. Maor R, Shirasu K (2005) The arms race continues: battle strategies between plants and fungal pathogens. Curr Opin Microbiol 8:399–404

    Article  CAS  Google Scholar 

  28. Perret X, Staehelin C, Broughton WJ (2000) Molecular basis of symbiotic promiscuity. Microbiol Mol Biol Rev 64:180–201

    Article  CAS  Google Scholar 

  29. Dubrovsky EB, Dubrovskaya VA, Berger EM (2004) Hormonal regulation and functional role of Drosophila E75A orphan nuclear receptor in the juvenile hormone signaling pathway. Dev Biol 268:258–270

    Article  CAS  Google Scholar 

  30. Dahanukar A, Hallem EA, Carlson JR (2005) Insect chemoreception. Curr Opin Neurobiol 15:423–430

    Article  CAS  Google Scholar 

  31. Bargmann CI, Hartwieg E, Horvitz HR (1993) Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74:515–527

    Article  CAS  Google Scholar 

  32. Chuang CF, Bargmann CI (2005) A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev 19:270–281

    Article  CAS  Google Scholar 

  33. Zhang Y, Lu H, Bargmann CI (2005) Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature 438:179–184

    Article  CAS  Google Scholar 

  34. Nuttley WM, Atkinson-Leadbeater KP, Van Der Kooy D (2002) Serotonin mediates food-odor associative learning in the nematode Caenorhabditis elegans. Proc Natl Acad Sci USA 99:12449–12454

    Article  CAS  Google Scholar 

  35. Beale E, Li G, Tan MW, Rumbaugh KP (2006) Caenorhabditis elegans senses bacterial autoinducers. Appl Environ Microbiol 72(7):5135–5137

    Article  CAS  Google Scholar 

  36. Darby C, Cosma CL, Thomas JH, Manoil C (1999) Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa. Proc Natl Acad Sci USA 96:15202–15207

    Article  CAS  Google Scholar 

  37. Tan MW, Rahme LG, Sternberg JA, Tompkins RG, Ausubel FM (1999) Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. Proc Natl Acad Sci USA 96:2408–2413

    Article  CAS  Google Scholar 

  38. Waring RH, Harris RM (2005) Endocrine disrupters: a human risk? Mol Cell Endocrinol 244:2–9

    Article  CAS  Google Scholar 

  39. Fox JE, Starcevic M, Jones PE, Burow ME, McLachlan JA (2004) Phytoestrogen signaling and symbiotic gene activation are disrupted by endocrine-disrupting chemicals. Environ Health Perspect 112:672–677

    Article  CAS  Google Scholar 

  40. Lyte M (2004) Microbial endocrinology and infectious disease in the 21st century. Trends Microbiol 12:14–20

    Article  CAS  Google Scholar 

  41. Sperandio V, Torres AG, Jarvis B, Nataro JP, Kaper JB (2003) Bacteria-host communication: the language of hormones. Proc Natl Acad Sci USA 100:8951–8956

    Article  CAS  Google Scholar 

  42. Telford G et al. (1998) The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-L-homoserine lactone has immunomodulatory activity. Infect Immun 66:36–42

    CAS  Google Scholar 

  43. Hooi DS, Bycroft BW, Chhabra SR, Williams P, Pritchard DI (2004) Differential immune modulatory activity of Pseudomonas aeruginosa quorum-sensing signal molecules. Infect Immun 72:6463–6470

    Article  CAS  Google Scholar 

  44. Ritchie AJ, Yam AO, Tanabe KM, Rice SA, Cooley MA (2003) Modification of in vivo and in vitro T- and B-cell-mediated immune responses by the Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone. Infect Immun 71:4421–4431

    Article  CAS  Google Scholar 

  45. Ritchie AJ et al. (2005) The Pseudomonas aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone inhibits T-cell differentiation and cytokine production by a mechanism involving an early step in T-cell activation. Infect Immun 73:1648–1655

    Article  CAS  Google Scholar 

  46. Pritchard DI et al. (2005) Alleviation of insulitis and moderation of diabetes in NOD mice following treatment with a synthetic Pseudomonas aeruginosa signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone. Acta Diabetol 42:119–122

    Article  CAS  Google Scholar 

  47. Smith RS et al. (2001) 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-kappa B and activator protein-2. J Immunol 167:366–374

    CAS  Google Scholar 

  48. Smith RS, Kelly R, Iglewski BH, Phipps RP (2002) The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation. J Immunol 169:2636–2642

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  50. Shiner EK et al. (2006) Pseudomonas aeruginosa autoinducer modulates host cell response through calcium signaling. Cell Microbiol (in press)

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

    Article  CAS  Google Scholar 

  52. Horikawa M et al. (2006) Synthesis of Pseudomonas quorum-sensing autoinducer analogs and structural entities required for induction of apoptosis in macrophages. Bioorg Med Chem Lett 16:2130–2133

    Article  CAS  Google Scholar 

  53. Li L, Hooi D, Chhabra SR, Pritchard D, Shaw PE (2004) Bacterial N-acylhomoserine lactone-induced apoptosis in breast carcinoma cells correlated with down-modulation of STAT3. Oncogene 23(28):4894–4902

    Article  CAS  Google Scholar 

  54. Ranger AM, Malynn BA, Korsmeyer SJ (2001) Mouse models of cell death. Nat Genet 28:113–118

    Article  CAS  Google Scholar 

  55. Singh PK et al. (2000) Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407:762–764

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  57. Favre-Bonte S et al. (2002) Detection of Pseudomonas aeruginosa cell-to-cell signals in lung tissue of cystic fibrosis patients. Microb Pathog 32:143–147

    Article  CAS  Google Scholar 

  58. Middleton B et al. (2002) Direct detection of N-acylhomoserine lactones in cystic fibrosis sputum. FEMS Microbiol Lett 207:1–7

    Article  CAS  Google Scholar 

  59. Pearson JP et al. (1994) Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc Natl Acad Sci USA 91:197–201

    Article  CAS  Google Scholar 

  60. Charlton TS et al. (2000) 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

    Article  CAS  Google Scholar 

  61. Haynes A 3rd et al. (2005) Syndecan 1 shedding contributes to Pseudomonas aeruginosa sepsis. Infect Immun 73:7914–7921

    Article  CAS  Google Scholar 

  62. Imamura Y et al. (2004) Azithromycin inhibits MUC5AC production induced by the Pseudomonas aeruginosa autoinducer N-(3-oxododecanoyl) homoserine lactone in NCI-H292 Cells. Antimicrob Agents Chemother 48:3457–461

    Article  CAS  Google Scholar 

  63. Hill SJ (2006) G-protein-coupled receptors: past, present and future. Br J Pharmacol 147(Suppl 1):S27–S37

    Article  CAS  Google Scholar 

  64. Williams SC et al. (2004) Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells. J Bacteriol 186:2281–2287

    Article  CAS  Google Scholar 

  65. Fuqua C, Parsek MR, Greenberg EP (2001) Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu Rev Genet 35:439–468

    Article  CAS  Google Scholar 

  66. McKnight SL, Iglewski BH, Pesci EC (2000) The Pseudomonas quinolone signal regulates rhl quorum sensing in Pseudomonas aeruginosa. J Bacteriol 182:2702–2708

    Article  CAS  Google Scholar 

  67. Chen X et al. (2002) Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415:545–549

    Article  CAS  Google Scholar 

  68. Miller ST et al. (2004) Salmonella typhimurium recognizes a chemically distinct form of the bacterial quorum-sensing signal AI-2. Mol Cell 15:677–687

    Article  CAS  Google Scholar 

  69. Holden MT et al. (1999) Quorum-sensing cross talk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other Gram-negative bacteria. Mol Microbiol 33:1254–1266

    Article  CAS  Google Scholar 

  70. Kay RR, Dhokia B, Jermyn KA (1983) Purification of stalk-cell-inducing morphogens from Dictyostelium discoideum. Eur J Biochem 136:51–56

    Article  CAS  Google Scholar 

  71. Rasmussen TB, Givskov M (2006) Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol 296:149–161

    Article  CAS  Google Scholar 

  72. Motola DL et al. (2006) Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans. Cell 124:1209–1223

    Article  CAS  Google Scholar 

  73. Shiner EK, Rumbaugh KP, Williams SC (2005) Interkingdom signaling: deciphering the language of homoserine lactones. FEMS Microbiol Rev 29(5):935–947

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Work in K.P. Rumbaugh’s lab is supported by the American Lung Association. Many thanks to Simon Williams for his conceptual and editorial contributions.

Author information

Authors and Affiliations

  1. Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA

    Kendra P. Rumbaugh

Authors
  1. Kendra P. Rumbaugh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kendra P. Rumbaugh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rumbaugh, K.P. Convergence of hormones and autoinducers at the host/pathogen interface. Anal Bioanal Chem 387, 425–435 (2007). https://doi.org/10.1007/s00216-006-0694-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-006-0694-9

Keywords

Search

Navigation