In vitro antibiofilm efficacy of farnesol against Candida species

Abstract

Candida species are opportunistic fungi that can cause mucosal or invasive infections. Especially in biofilm-related infections, resistance is very high to anifungals; therefore more effective treatment strategies are needed. Farnesol(3,7,11-trimethyl-2,6,10-dodecatriene-1-ol) is the quorum sensing (QS) signal molecule and can interact with Candida species both as a QS molecule and as an exogenous agent. The aim of this study was to investigate the effects of farnesol on both the planktonic and biofilm forms of Candida species by colorimetric, microbiological, and electron microscopic methods. Obtained results demonstrated the inhibitory effect of farnesol on the planktonic and biofilm forms of Candida. Farnesol showed a biofilm-enhancing effect at lower concentrations. TEM findings showed the membrane and wall damage, vacuolization, or granulation in cells. SEM images confirmed biofilm reduction in pre-/post-biofilm applications as a result of farnesol treatment. In conclusion, farnesol can be used as an alternative agent to reduce the Candida biofilms, with future studies.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. Bezerra CF, de Alencar Júnior JG, de Lima HR, Dos Santos ATL, Pereira da Silva JC, Gusmão da Silva T, Leal ALAB, Rocha JE, de Freitas TS, Tavares Vieira TA, Bezerra MCF, Sales DL, Kerntopf MR, de Araujo DG, Filho JMB, Peixoto LR, Pinheiro AP, Ribeiro-Filho J, Coutinho HDM, Morais-Braga MFB, Gonçalves da Silva T (2020) Antifungal activity of farnesol incorporated in liposomes and associated with fluconazole. Chem Phys Lipids 233:104987. https://doi.org/10.1016/j.chemphyslip.2020.104987

    Article  PubMed  Google Scholar 

  2. Cavalheiro M, Teixeira MC (2018) Candida biofilms: threats, challenges, and promising strategies. Front Med 5:28

    Google Scholar 

  3. Chavez-Dozal AA, Nourabadi N, Erken M, McDougald D, Nishiguchi MK (2016) Comparative analysis of quantitative methodologies for Vibrionaceae biofilms. Folia Microbiol 61(6):449–453

    Google Scholar 

  4. Clinical and Laboratory Standards Institute (National Committee for Clinical Laboratory Standards)(2002) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved StandardM27-A2, 2nd ed, NCCLS: Wayne, PA, USA

  5. Cordeiro RDA, Pereira LMG, de Sousa JK, Serpa R, Andrade ARC, Portela FVM, Evangelista AJJ, Sales JA, Aguiar ALR, Mendes PBL at al. (2019) Farnesol inhibits planktonic cells and antifungal-tolerant biofilms of Trichosporon asahii and Trichosporon inkin. Med Mycol 57(8):1038–1045

    PubMed  Google Scholar 

  6. Corte L, Casagrande Pierantoni D, Tascini C, Roscini L, Cardinali G (2019) Biofilm specific activity: a measure to quantify microbial biofilm. Microorganisms 7(3):73

    PubMed Central  Google Scholar 

  7. Decanis N, Tazi N, Correia A, Vilanova M, Rouabhia M (2011) Farnesol, a quorum-sensing molecule triggers Candida albicans morphological changes by downregulating the expression of different secreted aspartyl proteinase genes. Open Microbiol J 5:119–126

    PubMed  PubMed Central  Google Scholar 

  8. Derengowski LS, De-Souza-Silva C, Braz SV, Mello-De-Sousa TM, Bao SN (2009) Antimicrobial effect of farnesol, a Candida albicans quorum sensing molecule, on Paracoccidioides brasiliensis growth and morphogenesis. Ann Clin Microbiol Antimicrob 8(13):13

    PubMed  PubMed Central  Google Scholar 

  9. Dizova S, Bujdakova H (2017) Properties and role of the quorum sensing molecule farnesol in relation to the yeast Candida albicans. Pharmazie 72:307–312

    PubMed  Google Scholar 

  10. Donlan RM (2001) Biofilm formation: a clinically relevant microbiological process. Clin Infect Dis 33(8):1387–1392

    PubMed  Google Scholar 

  11. Douglas LJ (2003) Candida biofilms and their role in infection. Trends Microbiol 11(1):30–36

    PubMed  Google Scholar 

  12. Fazli M, Almblad H, Rybtke ML, Givskov M, Eberl L, Tolker-Nielsen T (2014) Regulation of biofilm formation in Pseudomonas and Burkholderia species. Environ Microbiol 16:1961–1981. https://doi.org/10.1111/1462-2920.12448

    Article  PubMed  Google Scholar 

  13. Fernandes RA, Monteiro AR, Arias LS, Fernandes GL, Delbem ACB, Barbosa DB (2016) Biofilm formation by Candida albicans and Streptococcus mutans in the presence of farnesol: a quantitative evaluation. Biofouling 32(3):329–338

    PubMed  Google Scholar 

  14. Ferreira AV, Prado CG, Carvalho RR, Dias KS, Dias AL (2013) Candida albicans and Non-C. albicans Candida Species: comparison of biofilm production and metabolic activity in biofilms, and putative virulence properties of isolates from hospital environments and infections. Mycopathologia 175:265–272

    PubMed  Google Scholar 

  15. Hasan F, Xess I, Wang X, Jain N, Fries BC (2009) Biofilm formation in clinical Candida isolates and its association with virulence. Microbes Infect 11(8-9):753–761

    PubMed  PubMed Central  Google Scholar 

  16. Jung YY, Hwang ST, Sethi G, Fan L, Arfuso F, Ahn KS (2018) Potential anti-inflammatory and anti-cancer properties of farnesol. Molecules 23(11):2827

    PubMed Central  Google Scholar 

  17. Katragkou A, McCarthy M, Alexander EL, Antachopoulos C, Meletiadis J, Jabra-Rizk MA, Petraitis V, Roilides E, Walsh TJ (2015) In vitro interactions between farnesol and fluconazole, amphotericin B or micafungin against Candida albicans biofilms. J Antimicrob Chemother 70(2):470–478

    PubMed  Google Scholar 

  18. Kovács R, Majoros L (2020) Fungal quorum-sensing molecules: a review of their antifungal effect against Candida Biofilms. J Fungi 6(3):99

    Google Scholar 

  19. Krom BP, Levy N, Meijler MM, Jabra-Rizk MA (2016) Farnesol and Candida albicans: quorum sensing or not quorum sensing? Israel J Chem 56(5):295–301

    Google Scholar 

  20. Kunyeit L, Kurrey NK, Anu-Appaiah KA, Rao RP (2019) Probiotic yeasts inhibit virulence of non-albicans Candida species. MBio 10(5):e02307–e02319

    PubMed  PubMed Central  Google Scholar 

  21. Langford ML, Hasim S, Nickerson KW, Atkin AL (2010) Activity and toxicity of farnesol towards Candida albicans are dependent on growth conditions. Antimicrob Agents Chemother 54(2):940–942

    PubMed  Google Scholar 

  22. Leonhardt I, Spielberg S, Weber M, Albrecht-Eckardt D, Blass M, Claus R, Barz D, Scherlach K, Hertweck C, Löffler J, Hünniger K, Kurzai O (2015) The fungal quorum sensing molecule farnesol activates innate immune cells but supresses cellular adaptive immunity. mBio 6(2):e00143

    PubMed  PubMed Central  Google Scholar 

  23. Lone SA, Ahmad A (2019) Candida auris—the growing menace to global health. Mycoses 62(8):620–637

    PubMed  Google Scholar 

  24. Monteiro DR, Arias LS, Fernandes RA, Deszo da Silva LF, de Castilho MOVF, da Rosa TO0, Vieira APM, Straioto FG, Barbosa DB, Delbem ACB (2017) Antifungal activity of tyrosol and farnesol used in combination against Candida species in the planktonic state or forming biofilms. J Appl Microbiol 123(2):392–400

    PubMed  Google Scholar 

  25. Nagy F, Vitális E, Jakab Á, Borman AM, Forgács L, Tóth Z, Majoros L, Kovács R (2020) In vitro and in vivo effect of exogenous farnesol exposure against Candida auris. Front Microbiol 11:957

    PubMed  PubMed Central  Google Scholar 

  26. Öztürk BY (2019) Intracellular and extracellular green synthesis of silver nanoparticles using Desmodesmus sp.: their Antibacterial and antifungal effects. Caryologia. Int J Cytol Cytosyst Cytogenet 72(1):29–43

    Google Scholar 

  27. Öztürk BY, Gürsu BY, Dağ İ (2020) Antibiofilm and antimicrobial activities of green synthesized silver nanoparticles using marine red algae Gelidium corneum. Process Biochem 89:208–219

    Google Scholar 

  28. Paluch E, Rewak-Soroczyńska J, Jędrusik I, Mazurkiewicz E, Jermakow K (2020) Prevention of biofilm formation by quorum quenching. Appl Microbiol Biotechnol 104(5):1871–1881

    PubMed  PubMed Central  Google Scholar 

  29. Pammi M, Liang R, Hicks JM, Barrish J, Versalovic J (2011) Farnesol decreases biofilms of Staphylococcus epidermidis and exhibits synergy with nafcillin and vancomycin. Pediatr Res 70(6):578–583

    PubMed  PubMed Central  Google Scholar 

  30. Prasad R, Kapoor K (2005) Multidrug resistance in yeast Candida. Int Rev Cytol 242:215–248

    PubMed  Google Scholar 

  31. Ramage G, Saville SP, Wickes BL, López-Ribot JL (2002) Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Appl Environ Microbiol 68(11):5459–5463

    PubMed  PubMed Central  Google Scholar 

  32. Ramage G, Saville SP, Thomas DP, López-Ribot J (2005) Candida biofilms: an update. Eukaryot Cell 4(4):633–638

    PubMed  PubMed Central  Google Scholar 

  33. Ramage G, Martínez JP, López-Ribot JL (2006) Candida biofilms on implanted biomaterials: a clinically significant problem. FEMS Yeast Res 6(7):979–986

    PubMed  Google Scholar 

  34. Rodrigues CF, Černáková L (2020) Farnesol and Tyrosol: Secondary metabolites with a crucial quorum-sensing role in Candida biofilm development. Genes 11(4):444

    PubMed Central  Google Scholar 

  35. Rossignol T, Logue ME, Reynolds K, Grenon M, Lowndes NF, Butler G (2007) Transcriptional response of Candida parapsilosis following exposure to farnesol. Antimicrob Agents Chemother 51(7):2304–2312

    PubMed  PubMed Central  Google Scholar 

  36. Sebaa S, Boucherit-Otmani Z, Courtois P (2019) Effects of tyrosol and farnesol on Candida albicans biofilm. Mol Med Rep 19(4):3201–3209

    PubMed  PubMed Central  Google Scholar 

  37. Sharma D, Misba L, Khan AU (2019) Antibiotics versus biofilm: an emerging battleground in microbial communities. Antimicrob Resist Infect Control 8(1):1–10

    Google Scholar 

  38. Solano C, Echeverz M, Lasa I (2014) Biofilm dispersion and quorum sensing. Curr Opin Microbiol 18:96–104

    PubMed  Google Scholar 

  39. Spampinato C, Leonardi D (2013) Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. Biomed Res Int 2013:204237

    PubMed  PubMed Central  Google Scholar 

  40. Taff HT, Nett JE, Andes DR (2012) Comparative analysis of Candida biofilm quantitation assays. Sabouraudia 50(2):214–218

    Google Scholar 

  41. Wu G, Yan S (2019) Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas aeruginosa? Front Microbiol 10:1582

    PubMed  PubMed Central  Google Scholar 

  42. Xia J, Qian F, Xu W, Zhang Z, Wei X (2017) In vitro inhibitory effects of farnesol and interactions between farnesol and antifungals against biofilms of Candida albicans resistant strains. Biofouling 33(4):283–293

    PubMed  Google Scholar 

  43. Yapar N (2014) Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag 10:95–105

    PubMed  PubMed Central  Google Scholar 

  44. Zhang L, Chang W, Sun B, Groh M, Speicher A, Lou H (2011) Bisbibenzyls, a new type of antifungal agent, inhibit morphogenesis switch and biofilm formation through upregulation of DPP3 in Candida albicans. PLoS One 6(12):e28953

    PubMed  PubMed Central  Google Scholar 

  45. Zhao LX, Li DD, Hu DD, Hu GH, Yan L, Wang Y, Jiang YY (2013) Effect of tetrandrine against Candida albicans biofilms. PLoS One 8(11)

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Bükay Yenice Gürsu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Verify currency and authenticity via CrossMark

Cite this article

Yapıcı, M., Gürsu, B.Y. & Dağ, İ. In vitro antibiofilm efficacy of farnesol against Candida species. Int Microbiol 24, 251–262 (2021). https://doi.org/10.1007/s10123-021-00162-4

Download citation

Keywords

  • Farnesol
  • Biofilm
  • Candida
  • Electron microscopy