Skip to main content

Advertisement

SpringerLink
Log in

An innovative role for tenoxicam as a quorum sensing inhibitor in Pseudomonas aeruginosa

  • Original Paper
  • Published:
Archives of Microbiology Aims and scope Submit manuscript

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen exhibiting higher resistance to commonly used antibiotics. Microbial resistance to antibiotics is a major problem that hinders attempts to control microbial infections. Quorum sensing inhibitors could help us solve such problem by repressing quorum sensing that controls the production of virulence factors in many pathogens including P. aeruginosa. In this study, the influence of tenoxicam, a non-steroidal anti-inflammatory drug, on quorum sensing in P. aeruginosa was characterized. Treatment of P. aeruginosa with tenoxicam decreased production of many virulence factors such as pyoverdin, rhamnolipids, pyocyanin, elastase, proteases, and hemolysins. Moreover, qRT-PCR revealed a significant reduction in expression of quorum sensing genes in tenoxicam-treated P. aeruginosa in comparison with untreated bacteria. Tenoxicam markedly reduced the capacity of P. aeruginosa to kill mice infection model. Mice injected with tenoxicam-treated P. aeruginosa exhibited higher survival rate as compared with those inoculated with untreated bacteria. Current data clearly demonstrate that tenoxicam has quorum sensing inhibitory effect on P. aeruginosa. Tenoxicam could play a role in reduction of Pseudomonas quorum sensing-dependant virulence factors production, and therefore affect its pathogenesis in the host. In summary, the current study suggests that tenoxicam could be used as adjuvant to antibiotics in the management of diseases caused by P. aeruginosa.

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. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Abbas HA (2015) Inhibition of virulence factors of Pseudomonas aeruginosa by diclofenac sodium. Roum Arch Microbiol Immunol 74:79–85

    CAS  PubMed  Google Scholar 

  • Antunes LC, Ferreira RB, Buckner MM (2010) Quorum sensing in bacterial virulence. Microbiology 156:2271–2282

    CAS  PubMed  Google Scholar 

  • Bjarnsholt T, Jensen OP, Jakobsen TH, Phipps R, Nielsen AK, Rybtke MT et al (2010) Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients. PLoS One 5:e10115

    PubMed  PubMed Central  Google Scholar 

  • Chanda W, Joseph TP, Padhiar AA (2017) Combined effect of linolenic acid and tobramycin on Pseudomonas aeruginosa biofilm formation and quorum sensing. Exp Ther Med 14:4328–4338

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chow S, Gu K, Jiang L, Nassour A (2011) Salicylic acid affects swimming, twitching and swarming motility in Pseudomonas aeruginosa, resulting in decreased biofilm formation. J Exp Microbiol Immunol 15:22–29

    Google Scholar 

  • Clinical and Laboratory Standards Institute (CLSI) (2012) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, approved standard, CLSI Document M07-A9, Vol. 32, No. 3. Wayne, PA, USA

  • Deep A, Chaudhary U, Gupta V (2011) Quorum sensing and bacterial pathogenicity from molecules to disease. J Lab Physicians 3:4–11

    CAS  PubMed  PubMed Central  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Elbossaty WF (2017) Antibiotic drugs and multidrug resistance bacteria. Int J Pub Health Safe 2:131

    Google Scholar 

  • El-Mowafy SA, Abd El-Galil KH, El-Messry SM, Shaaban MI (2014) Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa. Microb Pathog 74:25–32

    CAS  PubMed  Google Scholar 

  • El-Shaer S, Shaaban M, Barwa R, Hassan R (2016) Control of quorum sensing and virulence factors of Pseudomonas aeruginosa using phenylalanine arginyl β-naphthylamide. J Med Microbiol 65:1194–1204

    CAS  PubMed  Google Scholar 

  • Essar DW, Eberly L, Hadero A, Crawford IP (1990) Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: interchangeability of the two anthranilate synthases and evolutionary implications. J Bacteriol 172:884–900

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fischbach MA, Walsh CT (2009) Antibiotics for emerging pathogens. Science 325:1089–1093

    CAS  PubMed  PubMed Central  Google Scholar 

  • Geske GD, Mattmann ME, Blackwell HE (2008) Evaluation of a focused library of N-aryl-homoserine lactones reveals a new set of potent quorum sensing modulators. Bioorg Med Chem Lett 18:5978–5981

    CAS  PubMed  PubMed Central  Google Scholar 

  • Givskov M, De-Nys R, Manefield M, Gram L, Maximilien R, Eberl L et al (1996) Eukaryotic interference with homoserine lactone-mediated prokaryotic signaling. J Bacteriol 178:6618–6622

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta RK, Setia S, Harjai K (2011) Expression of Quorum sensing and virulence factors are interlinked in Pseudomonas aeruginosa: an in vitro approach. Am J Biomed Sci 3:116–125

    CAS  Google Scholar 

  • Hentzer M, Riedel K, Rasmussen TB, Heydorn A, Andersen JB, Parsek MR et al (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148:87–102

    CAS  PubMed  Google Scholar 

  • Hentzer M, Wu H, Andersen JB, Riedel K, Rasmussen TB, Bagge N et al (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. Eur Mol Biol Org J 22:3803–3815

    CAS  Google Scholar 

  • Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA et al (2008) NHSN annual update: antimicrobial resistant pathogens associated with healthcare-associated infections. Infect Control Hosp Epidemiol 29:996–1011

    PubMed  Google Scholar 

  • Jimenez PN, Koch G, Thompson JA, Xavier KB, Cool RH, Quax WJ (2012) The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev 76:46–65

    CAS  PubMed  Google Scholar 

  • Kalyani ALT, Naga-Sireesha G, Aditya AKG, Girija Sankar G (2014) Isolation and antimicrobial activity of rhamnolipid (biosurfactant) from oil-contaminated soil sample using humic-acid salts-vitamin agar. Int J Res Eng Tech 3:357–365

    Google Scholar 

  • Khalifa AB, Moissenet D, Thien VH, Khedher M (2011) Virulence factors in Pseudomonas aeruginosa. Ann Biol Clin 69:393–403

    Google Scholar 

  • Khodaverdian V, Pesho M, Truitt B, Bollingera L, Patela P, Nithiananthama S et al (2013) Discovery of Anti-virulence agents against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 57:3645–3652

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim H, Lee S, Byun Y, Park H (2015) 6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Sci Rep 5:8656

    CAS  PubMed  PubMed Central  Google Scholar 

  • Koneman EW, Allen SD, Janda WM, Scheckenberger PC, Winn WC (2006) Color atlas and textbook of diagnostic microbiology, 6th edn. Lippincott, Philadelphia

    Google Scholar 

  • Lazdunski AM, Ventre I, Sturgis JN (2004) Regulatory circuits and communication in gram-negative bacteria. Nat Rev Microbiol 2:581–592

    CAS  PubMed  Google Scholar 

  • Lesic B, Lépine F, Déziel E, Zhang J, Zhang Q, Padfield K, Castonguay M, Milot S, Stachel S, Tzika AA, Tompkins RG, Rahme LG (2007) Inhibitors of pathogen intercellular signals as selective anti-infective compounds. PLoS Pathog 3:e126

    PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−∆∆CT method. Methods 25:402–408

    CAS  PubMed  Google Scholar 

  • Marshall J (2013) Quorum sensing. Proc Natl Acad Sci USA 110:8

    Google Scholar 

  • Mohabi S, Kalantar-Neyestanaki D, Mansouri S (2017) Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa by Quercus infectoria gall extracts. Iran J Microbiol 9:26–32

    PubMed  PubMed Central  Google Scholar 

  • Moradali MF, Ghods S, Rehm BHA (2017) Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol 7:39

    PubMed  PubMed Central  Google Scholar 

  • Nalca Y, Jansch L, Bredenbruch F, Geffers R, Buer J, Häussler S (2006) Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1, a global approach. Antimicrob Agents Chemother 50:1680–1688

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ni N, Li M, Wang J, Wang B (2009) Inhibitors and antagonists of bacterial quorum sensing. Med Res Rev 29:65–124

    CAS  PubMed  Google Scholar 

  • Ohman DE, Cryz SJ, Iglewski BH (1980) Isolation and characterization of a Pseudomonas aeruginosa PAO1 mutant that produces altered elastase. J Bacteriol 142:836–884

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ouyang J, Sun F, Feng W, Sun Y, Qiu X, Xiong L et al (2016) Quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors in Pseudomonas aeruginosa. J Appl Microbiol 120:966–974

    CAS  PubMed  Google Scholar 

  • Pesci EC, Milbank JB, Pearson JP, McKnight S, Kende AS, Greenberg EP et al (1999) Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 96:11229–11234

    CAS  PubMed  PubMed Central  Google Scholar 

  • Prateeksha Singh BR, Shoeb M (2017) Scaffold of selenium nanovectors and honey phytochemicals for inhibition of Pseudomonas aeruginosa quorum sensing and biofilm formation. Front Cell Infect Microbiol 7:1–14

    Google Scholar 

  • Prithiviraj B, Bais HP, Weir T, Suresh B, Najarro EH, Dayakar BV et al (2005) Down-regulation of virulence factors of Pseudomonas aeruginosa by salicylic acid attenuates its virulence on Arabidopsis thaliana and Caenorhabditis elegans. Infect Immun 73:5319–5328

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rasko DA, Sperandio V (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat Rev Drug Discov 9:117–128

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Rasmussen BT, Skindersoe EM, Jarnsholt BT, Phipps RK, Christensen KB, Jensen PO et al (2005) Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 151:1325–1340

    CAS  PubMed  Google Scholar 

  • Singh VK, Mishra A, Jha B (2017) Anti-quorum sensing and anti-biofilm activity of Delftia tsuruhatensis extract by attenuating the quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa. Front Cell Infect Microbiol 7:1–16

    Google Scholar 

  • Skindersoe ME, Alhede M, Phipps R, Yang L, Jensen PO, Rasmussen TB et al (2008) Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa. Antimicrob Agents Chemother 52:3648–3663

    CAS  PubMed  PubMed Central  Google Scholar 

  • Veesenmeyer JL, Hauser AR, Lisboa T, Rello J (2009) Pseudomonas aeruginosa virulence and therapy: evolving translational strategies. Crit Care Med 37:1777–1786

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the members of Medical Research Center, Cairo, Egypt for their help in mice survival experiment.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

    Momen Askoura & Hisham Abbas

  2. Department of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said, Egypt

    Moustafa Saleh

Authors
  1. Momen Askoura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moustafa Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hisham Abbas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Momen Askoura.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The animal study was approved by The Institutional Animal Care and Use Committee, Zagazig University (ZU-IACUC). All animals were handled according to guidelines from the Animal Ethics Board (Zagazig University). All participants provided written informed consent prior to enrolment in the study.

Additional information

Communicated by Erko Stackebrandt.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Askoura, M., Saleh, M. & Abbas, H. An innovative role for tenoxicam as a quorum sensing inhibitor in Pseudomonas aeruginosa. Arch Microbiol 202, 555–565 (2020). https://doi.org/10.1007/s00203-019-01771-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00203-019-01771-4

Keywords

Search

Navigation