Skip to main content

Advertisement

Log in

Pseudomonas aeruginosa pvdQ Gene Prevents Caco-2 Cells from Obstruction of Quorum-Sensing Signal

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Quorum sensing (QS) system plays an important role in bacterial pathopoiesis of incurable Pseudomonas aeruginosa infection, which strongly warrants new strategies for absence of curative treatment to date. Latest investigations show that pvdQ gene of P. aeruginosa can attenuate the pathopoiesis of the bacteria by encoding acylase enzyme and hydrolyze N-(3-oxododecanoyl)-Homoserine Lactone (3O-oxo-C12-HSL), the key signal molecule of QS system. This study tries to resist the pathogenicity of P. aeruginosa by transfecting human intestinal epithelial Caco-2 cells with pvdQ gene. We found that 3O-oxo-C12-HSL was decreased in the supernatant of cells transfected with pvdQ gene. Moreover, the result of flow cytometry showed that the 3O-oxo-C12-HSL evoked apoptosis rate of Caco-2 cells was inhibited when the cells were transfected with pvdQ gene. In contrast, the control result displayed increased Caco-2 cells’ apoptosis rate after stimulation of 3O-oxo-C12-HSL without protection of pvdQ gene. In conclusion, we successfully protect mammalian cells Caco-2 from injure of QS signal molecule 3O-oxo-C12-HSL through imputing pvdQ gene, which may suggest a new therapeutic strategy for P. aeruginosa infection.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bjarnsholt T, Givskov M (2007) Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens. Philos Trans R Soc Lond B 362:1213–1222

    Article  CAS  Google Scholar 

  2. Chhabra SR, Harty C, Hooi DS, Daykin M, Williams P, Telford G, Pritchard DI, Bycroft BW (2003) Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-l-homoserine lactone as immune modulators. J Med Chem 46:97–104

    Article  CAS  PubMed  Google Scholar 

  3. Chun CK, Ozer EA, Welsh MJ, Zabner J, Greenberg EP (2004) Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia. Proc Natl Acad Sci USA 101:3587–3590

    Article  CAS  PubMed  Google Scholar 

  4. De Lamo Marin S, Xu Y, Meijler MM, Janda KD (2007) Antibody catalyzed hydrolysis of a quorum sensing signal found in Gram-negative bacteria. Bioorg Med Chem Lett 17:1549–1552

    Article  PubMed  Google Scholar 

  5. DiMango E, Zar HJ, Bryan R, Prince A (1995) Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8. J Clin Invest 96:2204–2210

    Article  CAS  PubMed  Google Scholar 

  6. Dong YH, Xu JL, Li XZ, Zhang LH (2000) AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora. Proc Natl Acad Sci USA 97:3526–3531

    Article  CAS  PubMed  Google Scholar 

  7. Dong YH, Wang LH, Xu JL, Zhang HB, Zhang XF, Zhang LH (2001) Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature 411:813–817

    Article  CAS  PubMed  Google Scholar 

  8. Hancock RE (1998) Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria. Clin Infect Dis 27 Suppl 1:S93–S99

    Article  CAS  PubMed  Google Scholar 

  9. Hastings JW (2004) Bacterial quorum-sensing signals are inactivated by mammalian cells. Proc Natl Acad Sci USA 101:3993–3994

    Article  CAS  PubMed  Google Scholar 

  10. Hentzer M, Riedel K, Rasmussen TB, Heydorn A, Andersen JB, Parsek MR, Rice SA, Eberl L, Molin S, Hoiby N, Kjelleberg S, Givskov M (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148:87–102

    CAS  PubMed  Google Scholar 

  11. Huang JJ, Han JI, Zhang LH, Leadbetter JR (2003) Utilization of acyl-homoserine lactone quorum signals for growth by a soil pseudomonad and Pseudomonas aeruginosa PAO1. Appl Environ Microbiol 69:5941–5949

    Article  CAS  PubMed  Google Scholar 

  12. Huang JJ, Petersen A, Whiteley M, Leadbetter JR (2006) Identification of QuiP, the product of gene PA1032, as the second acyl-homoserine lactone acylase of Pseudomonas aeruginosa PAO1. Appl Environ Microbiol 72:1190–1197

    Article  CAS  PubMed  Google Scholar 

  13. Ishida T, Ikeda T, Takiguchi N, Kuroda A, Ohtake H, Kato J (2007) Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopentylamides. Appl Environ Microbiol 73:3183–3188

    Article  CAS  PubMed  Google Scholar 

  14. Kohler JE, Zaborina O, Wu L, Wang Y, Bethel C, Chen Y, Shapiro J, Turner JR, Alverdy JC (2005) Components of intestinal epithelial hypoxia activate the virulence circuitry of Pseudomonas. Am J Physiol Gastrointest Liver Physiol 288:G1048–G1054

    Article  CAS  PubMed  Google Scholar 

  15. Kumari A, Pasini P, Daunert S (2008) Detection of bacterial quorum sensing N-acyl homoserine lactones in clinical samples. Anal Bioanal Chem 391:1619–1627

    Article  CAS  PubMed  Google Scholar 

  16. Lamont IL, Martin LW (2003) Identification and characterization of novel pyoverdine synthesis genes in Pseudomonas aeruginosa. Microbiology 149:833–842

    Article  CAS  PubMed  Google Scholar 

  17. 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 23:4894–4902

    Article  CAS  PubMed  Google Scholar 

  18. Li G, Dong S, Qu J, Sun Z, Huang Z, Ye L, Liang H, Ai X, Zhang W, Chen X (2009) Synergism of hydroxyapatite nanoparticles and recombinant mutant human tumour necrosis factor-alpha in chemotherapy of multidrug-resistant hepatocellular carcinoma. Liver Int 30:585–592

    Article  CAS  PubMed  Google Scholar 

  19. Lin YH, Xu JL, Hu J, Wang LH, Ong SL, Leadbetter JR, Zhang LH (2003) Acyl-homoserine lactone acylase from Ralstonia strain XJ12B represents a novel and potent class of quorum-quenching enzymes. Mol Microbiol 47:849–860

    Article  PubMed  Google Scholar 

  20. Overhage J, Bains M, Brazas MD, Hancock RE (2008) Swarming of Pseudomonas aeruginosa is a complex adaptation leading to increased production of virulence factors and antibiotic resistance. J Bacteriol 190:2671–2679

    Article  CAS  PubMed  Google Scholar 

  21. Park SY, Kang HO, Jang HS, Lee JK, Koo BT, Yum DY (2005) Identification of extracellular N-acylhomoserine lactone acylase from a Streptomyces sp. and its application to quorum quenching. Appl Environ Microbiol 71:2632–2641

    Article  CAS  PubMed  Google Scholar 

  22. Pesci EC, Pearson JP, Seed PC, Iglewski BH (1997) Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa. J Bacteriol 179:3127–3132

    CAS  PubMed  Google Scholar 

  23. Shiner EK, Terentyev D, Bryan A, Sennoune S, Martinez-Zaguilan R, Li G, Gyorke S, Williams SC, Rumbaugh KP (2006) Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling. Cell Microbiol 8:1601–1610

    Article  CAS  PubMed  Google Scholar 

  24. Sio CF, Otten LG, Cool RH, Diggle SP, Braun PG, Bos R, Daykin M, Camara M, Williams P, Quax WJ (2006) Quorum quenching by an N-acyl-homoserine lactone acylase from Pseudomonas aeruginosa PAO1. Infect Immun 74:1673–1682

    Article  CAS  PubMed  Google Scholar 

  25. Smith RS, Iglewski BH (2003) P. aeruginosa quorum-sensing systems and virulence. Curr Opin Microbiol 6:56–60

    Article  CAS  PubMed  Google Scholar 

  26. Smith RS, Fedyk ER, Springer TA, Mukaida N, Iglewski BH, Phipps RP (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  PubMed  Google Scholar 

  27. 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  PubMed  Google Scholar 

  28. Swift S, Downie JA, Whitehead NA, Barnard AM, Salmond GP, Williams P (2001) Quorum sensing as a population-density-dependent determinant of bacterial physiology. Adv Microb Physiol 45:199–270

    Article  CAS  PubMed  Google Scholar 

  29. Van Delden C, Iglewski BH (1998) Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerg Infect Dis 4:551–560

    Article  PubMed  Google Scholar 

  30. Vikstrom E, Magnusson KE, Pivoriunas A (2005) The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone stimulates phagocytic activity in human macrophages through the p38 MAPK pathway. Microbes Infect 7:1512–1518

    Article  PubMed  Google Scholar 

  31. Vikstrom E, Tafazoli F, Magnusson KE (2006) Pseudomonas aeruginosa quorum sensing molecule N-(3 oxododecanoyl)-l-homoserine lactone disrupts epithelial barrier integrity of Caco-2 cells. FEBS Lett 580:6921–6928

    Article  PubMed  Google Scholar 

  32. Vikstrom E, Bui L, Konradsson P, Magnusson KE (2009) The junctional integrity of epithelial cells is modulated by Pseudomonas aeruginosa quorum sensing molecule through phosphorylation-dependent mechanisms. Exp Cell Res 315:313–326

    Article  PubMed  Google Scholar 

  33. Whitehead NA, Barnard AM, Slater H, Simpson NJ, Salmond GP (2001) Quorum-sensing in Gram-negative bacteria. FEMS Microbiol Rev 25:365–404

    Article  CAS  PubMed  Google Scholar 

  34. Williams SC, Patterson EK, Carty NL, Griswold JA, Hamood AN, Rumbaugh KP (2004) Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells. J Bacteriol 186:2281–2287

    Article  CAS  PubMed  Google Scholar 

  35. Xu F, Byun T, Deussen HJ, Duke KR (2003) Degradation of N-acylhomoserine lactones, the bacterial quorum-sensing molecules, by acylase. J Biotechnol 101:89–96

    Article  CAS  PubMed  Google Scholar 

  36. Zimmermann S, Wagner C, Muller W, Brenner-Weiss G, Hug F, Prior B, Obst U, Hansch GM (2006) Induction of neutrophil chemotaxis by the quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone. Infect Immun 74:5687–5692

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by National Natural Science Foundation of China (30873189), China National 973 project (MOST, 2007CB512900).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jianxin Song.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ye, L., Li, G., Li, H. et al. Pseudomonas aeruginosa pvdQ Gene Prevents Caco-2 Cells from Obstruction of Quorum-Sensing Signal. Curr Microbiol 62, 32–37 (2011). https://doi.org/10.1007/s00284-010-9668-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-010-9668-4

Keywords

Navigation