Skip to main content

Advertisement

SpringerLink
Log in

Inhibitory effects of novel 1,4-disubstituted 1,2,3-triazole compounds on quorum-sensing of P. aeruginosa PAO1

  • Brief Report
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Quorum sensing (QS) inhibition is an essential strategy to combat bacterial infection. Previously, we have synthesized a series of thymidine derivatives bearing isoxazole and 1,2,3-triazole rings (TITL). Herein, the inhibitory effects of TITL on QS of Pseudomonas aeruginosa PAO1 were evaluated. In vitro results demonstrated that TITL effectively inhibited biofilm formation and reduced the virulence factors of P. aeruginosa PAO1. In combination with antibiotics, our TITL compounds significantly prolonged the lifespans of Caenorhabditis elegans N2 nematodes that were infected with P. aeruginosa PAO1 in vivo. In conclusion, TITL compounds are promising candidates for the treatment of antibiotic-resistant P. aeruginosa PAO1.

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
Fig. 8

References

  1. Struss AK, Nunes A, Waalen J, Lowery CA, Pullanikat P, Denery JR, Conrad DJ, Kaufmann GF, Janda KD (2013) Toward implementation of quorum sensing autoinducers as biomarkers for infectious disease states. Anal Chem 85(6):3355–3362

    Article  CAS  Google Scholar 

  2. Chua SL, Yam JK, Hao P, Adav SS, Salido MM, Liu Y, Givskov M, Sze SK, Tolker NT, Yang L (2016) Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. Nat Commun 7:10750

    Article  CAS  Google Scholar 

  3. Gholamrezazadeh M, Shakibaie MR, Monirzadeh F, Masoumi S, Hashemizadeh Z (2018) Effect of nano-silver, nano-copper, deconex and benzalkonium chloride on biofilm formation and expression of transcription regulatory quorum sensing gene (rh1R) in drug-resistance Pseudomonas aeruginosa burn isolates. Burns 44(3):700–708

    Article  Google Scholar 

  4. Hentzer M, Givskov M (2003) Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest 112(9):1300–1307

    Article  CAS  Google Scholar 

  5. Schuster M, Greenberg EP (2006) A network of networks: quorum-sensing gene regulation in Pseudomonas aeruginosa. Int J Med Microbiol 296(2–3):73–81

    Article  CAS  Google Scholar 

  6. Li H, Li X, Song C, Zhang Y, Wang Z, Liu Z, Wei H, Yu J (2017) Autoinducer-2 facilitates Pseudomonas aeruginosa PAO1 pathogenicity in vitro and in vivo. Front Microbiol 8:1944

    Article  Google Scholar 

  7. Yin SL, Cang YJ, Deng SP, Wang QC, Yu WG, Gong QH (2011) Research progress of new antibacterial drugs that target bacterial quorum sensing systems. Acta Pharm Sin 46(6):613–621

    CAS  Google Scholar 

  8. Zhao M, Yu Y, Hua Y, Feng F, Tong Y, Yang X, Xiao J, Song H (2013) Design, synthesis and biological evaluation of N-sulfonyl homoserine lactone derivatives as inhibitors of quorum sensing in Chromobacterium violaceum. Molecules 18(3):3266–3278

    Article  CAS  Google Scholar 

  9. Barbachyn MR, Cleek GJ, Dolak LA, Garmon SA, Morris J, Seest EP, Thomas RC, Toops DS, Watt W, Wishka DG, Ford CW, Zurenko GE, Hamel JC, Schaadt RD, Stapert D, Yagi BH, Adams WJ, Friis JM, Slatter JG, Sams JP, Oien NL, Zaya MJ, Wienkers LC, Wynalda MA (2003) Identification of phenylisoxazolines as novel and viable antibacterial agents active against gram-positive pathogens. J Med Chem 46(2):284–302

    Article  CAS  Google Scholar 

  10. Ali OM, Amr AEE, Mostafa EE (2014) Synthesis and antimicrobial of some new substituted tetrazolomethylbenzo[d]-[1–3]triazole derivatives using 1Hbenzo[d][1–3]triazole as starting material. Res Chem Intermed 40:1545–1556

    Article  CAS  Google Scholar 

  11. Miyakoshi H, Miyahara S, Yokogawa T, Endoh K, Muto T, Yano W, Wakasa T, Ueno H, Chong KT, Taguchi J, Nomura M, Takao Y, Fujioka A, Hashimoto A, Itou K, Yamamura K, Shuto S, Nagasawa H, Fukuoka M (2012) 1,2,3-Triazole-containing uracil derivatives with excellent pharmacokinetics as a novel class of potent human deoxyuridine triphosphatase inhibitors. J Med Chem 55(14):6427–6437

    Article  CAS  Google Scholar 

  12. Gupta RA, Kaskhedikar SG (2013) Synthesis, antitubercular activity, and QSAR analysis of substituted nitroaryl analogs: chalcone, pyrazole, isoxazole, and pyrimidines. Med Chem Res 22(8):3863–3880

    Article  CAS  Google Scholar 

  13. O’Brien KT, Noto JG, O’Neill LN, Perez LJ (2015) Potent irreversible inhibitors of lasr quorum sensing in Pseudomonas aeruginosa. ACS Med Chem Lett 6(2):162–167

    Article  Google Scholar 

  14. Igarashi Y, Yamamoto K, Fukuda T, Shojima A, Nakayama J, Carro L, Trujillo ME (2015) Arthroamide, a cyclic depsipeptide with quorum sensing inhibitory activity from arthrobacter sp. J Nat Prod 78(11):2827–2831

    Article  CAS  Google Scholar 

  15. Zhang DW, Zhang YM, Li J, Zhao TQ, Gu Q, Lin F (2017) Ultrasonic-assisted synthesis of 1,4-disubstituted 1,2,3 triazoles via various terminal acetylenes and azide and their quorum sensing inhibition. Ultrason Sonochem 36:343–353

    Article  CAS  Google Scholar 

  16. Peeters E, Nelis HJ, Coenye T (2009) In vitro activity of ceftazidime, ciprofloxacin, meropenem, minocycline, tobramycin and trimethoprim-sulfamethoxazole against planktonic and sessile Burkholderia cepacia complex bacteria. J Antimicrob Chemoth 64(4):801–809

    Article  CAS  Google Scholar 

  17. Guo Q, Wei Y, Xia B, Jin Y, Liu C, Pan X, Shi J, Zhu F, Li J, Qian L, Liu X, Cheng Z, Jin S, Lin J, Wu W (2016) Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa. Sci Rep 6:19141

    Article  CAS  Google Scholar 

  18. O’Toole GA, Kolter R (1998) Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 30(2):295–304

    Article  Google Scholar 

  19. 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(2):884–900

    Article  CAS  Google Scholar 

  20. Pearson JP, Pesci EC, Iglewski BH (1997) Roles of Pseudomonas aeruginosa Las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes. J Bacteriol 179(18):5756–5767

    Article  CAS  Google Scholar 

  21. Grosso-Becerra MV (2016) Pseudomonas aeruginosa ATCC 9027 is a non-virulent strain suitable for mono-rhamnolipids production. Appl Microbiol Biotechnol 100(23):9995–10004

    Article  CAS  Google Scholar 

  22. Prithiviraj B, Bais HP, Weir T, Suresh B, Najarro EH, Dayakar BV, Schweizer HP, Vivanco JM (2005) Down regulation of virulence factors of Pseudomonas aeruginosa by salicylic acid attenuates its virulence on Arabidopsis thaliana and Caenorhabditis elegans. Infect Immun 73(9):5319–5328

    Article  CAS  Google Scholar 

  23. Hentzer M, Riedel K, Rasmussen TB, Heydorn A, Andersen JB, Parsek MR, Rice SA, Eberl L, Molin S, Høiby N, Kjelleberg S, Givskov M (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148(Pt 1):87–102

    Article  CAS  Google Scholar 

  24. Udrappa T, Bais HP (2008) Curcumin, a known phenolic from Curcuma Longa, attenua-tes the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models. J Agric Food Chem 56(6):1955–1962

    Article  Google Scholar 

  25. Rashid MH, Kornberg A (2000) Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 97(9):4885–4890

    Article  CAS  Google Scholar 

  26. Tan MW, Mahajan-Miklos S, Ausubel FM (1999) Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A 96(2):715–720

    Article  CAS  Google Scholar 

  27. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O (2010) Antibiotic resistance of bacterial biofilm. Int J Antimicrob 35(4):322–332

    Article  Google Scholar 

  28. 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

    Article  CAS  Google Scholar 

  29. Ben Hai Khalifa A, Moissenet D, Vu Thien H, Khedher M (2011) Virulence factors in Pseudomonas aeruginosa: mechanisms and modes of regulation. Ann Biol Clin (Paris) 69(4):393–403

    Google Scholar 

  30. Lee KM, Yoon MY, Park Y, Lee JH, Yoon SS (2011) Anaerobiosis-induced loss of cytotoxicity is due to inactivation of quorum sensing in Pseudomonas aeruginosa. Infect Immun 79(7):2792–2800

    Article  CAS  Google Scholar 

  31. Welsh MA, Eibergen NR, Moore JD, Blackwell HE (2015) Small molecule disruption of quorum sensing cross-regulation in Pseudomonas aeruginosa causes major and unexpected alterations to virulence phenotypes. J Am Chem Soc 137(4):1510–1519

    Article  CAS  Google Scholar 

  32. Ochsner UA, Reiser J (1995) Autoinducer mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 92(14):6424–6428

    Article  CAS  Google Scholar 

  33. Radji M, Agustama RA, Elya B, Tjampakasari CR (2013) Antimicrobial activity of green tea extract against isolates of methicillin-resistant Staphylococcus aureus and multi-drug resistant Pseudomonas aeruginosa. Asian Pac J Trop Biomed 3(8):663–667

    Article  CAS  Google Scholar 

  34. Romero R, Schaudinn C, Kusanovic JP, Gorur A, Gotsch F, Webster P, Nhan-Chang CL, Erez O, Kim CJ, Espinoza J, Goncalves LF, Vaisbuch E, Mazaki-Tovi S, Hassan SS, Costerton JW (2008) Detection of a microbial biofilm in intraamniotic infection. Am J Obstet Gynecol 198(1):1351–1355

    Article  Google Scholar 

  35. Stewart PS, Costerton JW (2001) Antibiotic resistance of bacteria in biofilms. Lancet 358(9276):135–138

    Article  CAS  Google Scholar 

  36. Brackman G, Cos P, Maes L, Nelis HJ, Coenye T (2011) Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics In Vitro and In Vivo. Antimicrob Agents Ch 55(6):2655–2661

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by the National Engineering Research Center for Strategic Drugs, Beijing Institute of Pharmacology and Toxicology Project of China (2018L0444J00093 and 2016L044J00004).

Author information

Author notes

  1. Shuang Li and Yumin Zhang contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China

    Shuang Li, Kai Jiang, Huiying Wang & Feng Lin

  2. College of Chemistry, Jilin University, Changchun, 130012, People’s Republic of China

    Yumin Zhang

Authors
  1. Shuang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yumin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kai Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huiying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Feng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Shuang Li, Yumin Zhang, and Feng Lin conceived and designed the experiments. Shuang Li performed the experiments. Shuang Li, Kai Jiang, and Huiying Wang analyzed and interpreted the data. Shuang Li wrote the initial draft of the manuscript draft. Feng Lin and Kai Jiang revised and edited the manuscript. All of the authors have approved the final manuscript.

Corresponding author

Correspondence to Feng Lin.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

No ethical approval was required for this study.

Additional information

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

Li, S., Zhang, Y., Jiang, K. et al. Inhibitory effects of novel 1,4-disubstituted 1,2,3-triazole compounds on quorum-sensing of P. aeruginosa PAO1. Eur J Clin Microbiol Infect Dis 40, 373–379 (2021). https://doi.org/10.1007/s10096-020-03998-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-020-03998-2

Keywords

Search

Navigation