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Quorum Sensing Signal Molecules Produced by Pseudomonas aeruginosa Cause Inflammation and Escape Host Factors in Murine Model of Urinary Tract Infection

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Abstract

Quorum sensing (QS) is well established for its role in pathogenesis of various infections of Pseudomonas aeruginosa. However, its role in local tissue damage during urinary tract infection (UTI) is not yet fully established. To have insight in this, the present study was planned. UTI was established in mice using standard strain PAO1 and its isogenic QS mutant JP2. One group was challenged only with QS signals. Damage was assessed in terms of histopathology and pathology markers, malondialdehyde (MDA) and reactive nitrogen intermediates (RNI). Effect on pathogen motility, uroepithelial adhesion, and host serum sensitivity was also ascertained. PAO1-infected mice showed severe inflammation and tissue destruction, while mice infected with JP2 showed no significant destruction. JP2 was also unable to mount any tissue pathology markers, MDA and RNI, whereas PAO1 showed significantly higher levels of these two. Presence of only QS signals also showed considerable renal pathology. Strain JP2 also showed less motility, reduced uroepithelial cell adhesion, and increased serum sensitivity. Result highlights that QS signals induce local tissue pathology along with interference of host protective mechanisms during UTI.

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Abbreviations

QS:

Quorum sensing

UTI:

Urinary tract infection

MDA:

Malondialdehyde

RNI:

Reactive nitrogen intermediates

HCl:

Hydrochloric acid

NaCl:

Sodium chloride

UEC:

Uroepithelial cell

PMNs:

Polymorphonuclear leucocytes

References

  1. Youn, Y.K., C. LaLonde, and R. Demling. 1992. The role of mediators in the response to thermal injury. World Journal of Surgery 16: 30–35.

    Article  PubMed  CAS  Google Scholar 

  2. McMillen, M.A., M. Huribal, M.E. Cunningham, R.J. Bala, W.E. Pleban, and M.L. D’Aiuto. 1996. Endothelin-1, interleukin-6, and interleukin-8 levels increase in patients with burns. The Journal of Burn Care & Rehabilitation 17: 384–390.

    Article  CAS  Google Scholar 

  3. Harris, B.H., and J.A. Gelfand. 1995. The immune response to trauma. Seminars in Pediatric Surgery 4: 77–82.

    PubMed  CAS  Google Scholar 

  4. Rumbaugh, K.P., A.N. Hamood, and J.A. Griswold. 2004. Cytokine induction by the P. aeruginosa quorum sensing system during thermal injury. Journal of Surgical Research 116: 137–144.

    Article  PubMed  CAS  Google Scholar 

  5. Leone, M., and J. Albanèse. 2003. J, Garniser F: Risk factors of nosocomial catheter associated urinary tract infection in a polyvalent intensive care unit. Intens Care Med 29(6): 929–32.

    Article  Google Scholar 

  6. Gupta, R.K., S. Setia, and K. Harjai. 2011. Expression of quorum sensing and virulence factors are interlinked in Pseudomonas aeruginosa: An in vitro approach. Am J Biomed Sci 3(2): 116–125.

    Article  CAS  Google Scholar 

  7. Boontham, P., A. Robins, P. Chandran, D. Pritchard, M. Cámara, P. Williams, S. Chuthapisith, C. Mckechnie, B.J. Rowlands, and O. Eremin. 2008. Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: Possible link in human sepsis. Clinl Sci 115: 343–351.

    Article  CAS  Google Scholar 

  8. Smith, R.S., S.G. Harris, R. Phipps, and B.H. Iglewski. 2002. The Pseudomonas aeruginosa quorum sensing molecule N-(3-oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo. Journal of Bacteriology 184(4): 1132–1139.

    Article  PubMed  CAS  Google Scholar 

  9. Nelson, L.K., G.H. D’Amours, K.M.S. Willoughby, D.W. Morck, and H. Ceri. 2009. Pseudomonas aeruginosa las and rhl quorum sensing systems are important for infection and inflammation in a rat prostatitis model. Microbiology 155: 2612–2619.

    Article  PubMed  CAS  Google Scholar 

  10. Mayer, M.L., J.A. Sheridan, C.J. Blohmke, S.E. Turvey, and R.E.W. Hancock. 2011. The Pseudomonas aeruginosa autoinducer 3O-C12 homoserine lactone provokes hyperinflammatory responses from cystic fibrosis airway epithelial cells. PLoS One 6(1): 1–9.

    Article  Google Scholar 

  11. Kumar, R., S. Chhibber, and K. Harjai. 2009. Quorum sensing is necessary for the virulence of Pseudomonas aeruginosa during urinary tract infection. Kid Internat 76: 286–292.

    Article  CAS  Google Scholar 

  12. Mittal, R., S. Sharma, S. Chhibber, and K. Harjai. 2006. Contribution of quorum sensing system to the virulence of P. aeruginosa in an experimental pyelonephritis model. Journal of Microbiology, Immunology and Infection 39: 302–309.

    Google Scholar 

  13. Taylor, P.W. 1983. Bactericidal and bacteriolytic action of serum against gram negative bacteria. Microbio Rev 47(1): 46–83.

    CAS  Google Scholar 

  14. Rashid, M.H., and A. Kornberg. 2004. Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 97: 4885–4890.

    Article  Google Scholar 

  15. Sharma, S., B.S. Madhur, R. Singh, and B.K. Sharma. 1987. Effect of contraceptive on adhesion of E. coli to uroepithelial cells. J Infec Dis 156(3): 490–496.

    Article  CAS  Google Scholar 

  16. Rumbaugh, K.P., J.A. Colmer, J.A. Griswold, and A.N. Hamood. 2001. The effects of infection of thermal injury by Pseudomonas aeruginosa PAO1 on the murine cytokine response. Cytokine 16: 160–170.

    Article  PubMed  CAS  Google Scholar 

  17. Rumbaugh, K.P., J.A. Griswold, B.H. Iglewski, and A.N. Hamood. 1999. Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infections. Infection and Immunity 67: 5854–5862.

    PubMed  CAS  Google Scholar 

  18. Lesprit, P., F. Faurisson, O. Join-Lambert, F. Roudot-Thoraval, M. Foglino, C. Vissuzaine, and C. Carbon. 2003. Role of the quorum-sensing system in experimental pneumonia due to Pseudomonas aeruginosa in rats. American Journal of Respiratory and Critical Care Medicine 167: 1478–1482.

    Article  PubMed  Google Scholar 

  19. Imamura, Y., K. Yanagihara, K. Tomono, H. Ohno, Y. Higashiyama, Y. Miyazaki, Y. Hirakata, Y. Mizuta, J.I. Kadota, K. Tsukamoto, and S. Kohno. 2005. Role of Pseudomonas aeruginosa quorum-sensing systems in a mouse model of chronic respiratory infection. Journal of Medical Microbiology 54: 515–518.

    Article  PubMed  Google Scholar 

  20. Zhu, H., S.J. Thuruthyil, and M.D.P. Willcox. 2002. Determination of quorum-sensing signal molecules and virulence factors of Pseudomonas aeruginosa isolates from contact lens-induced microbial keratitis. Journal of Medical Microbiology 51: 1063–1070.

    PubMed  CAS  Google Scholar 

  21. Tang, H.B., E. DiMango, R. Bryan, M. Gambello, B.H. Iglewski, J.B. Goldberg, and A. Prince. 1996. Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection. Infection and Immunity 64: 37–43.

    PubMed  CAS  Google Scholar 

  22. Sawa, T., M. Ohara, K. Kurahashi, S.S. Twining, D.W. Frank, D.B. Doroques, T. Long, M.A. Gropper, and J.P. Wiener-Kronish. 1998. In vitro cellular toxicity predicts Pseudomonas aeruginosa virulence in lung infections. Infection and Immunity 66: 3242–3249.

    PubMed  CAS  Google Scholar 

  23. Azghani, O., T. Bedinghaus, and R. Klein. 2000. Detection of elastase from Pseudomonas aeruginosa in sputum and its potential role in epithelial cell permeability. Lung 178: 181–189.

    Article  PubMed  CAS  Google Scholar 

  24. Davies, D.G., M.R. Parsek, J.P. Pearson, B.H. Iglewski, and J.W. Costerton. 1998. Greenberg, JP: The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280: 295–298.

    Article  PubMed  CAS  Google Scholar 

  25. O’Toole, G.A., and R. Kolter. 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Molec microbio 30(2): 295–304.

    Article  Google Scholar 

  26. Glessner, A., R.S. Smith, B.H. Iglewski, and J.B. Robinson. 1999. Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of twitching motility. Journal of Bacteriology 181: 1623–1629.

    PubMed  CAS  Google Scholar 

  27. Kohler, T., L.K. Curty, C. Barja, C. Van Delden, and J.C. Pechere. 2000. Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. Journal of Bacteriology 182: 5990–5996.

    Article  PubMed  CAS  Google Scholar 

  28. Klausen, M., A. Aaes-Jorgensen, S. Molin, and T. Tolker-Nielsen. 2003. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Molecular Microbiology 50: 61–68.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Kusum Harjai.

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Gupta, P., Gupta, R.K. & Harjai, K. Quorum Sensing Signal Molecules Produced by Pseudomonas aeruginosa Cause Inflammation and Escape Host Factors in Murine Model of Urinary Tract Infection. Inflammation 36, 1153–1159 (2013). https://doi.org/10.1007/s10753-013-9650-y

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