Advertisement

Inhibitory Effect of 5-Aminoimidazole-4-Carbohydrazonamides Derivatives Against Candida spp. Biofilm on Nanohydroxyapatite Substrate

  • C. Gabriel
  • L. GrenhoEmail author
  • F. Cerqueira
  • R. Medeiros
  • A. M. Dias
  • A. I. Ribeiro
  • M. F. Proença
  • M. H. Fernandes
  • J. C. Sousa
  • F. J. Monteiro
  • M. P. Ferraz
Original Article
  • 49 Downloads

Abstract

Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N′-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.

Graphic Abstract

Keywords

Imidazole derivatives Nanohydroxyapatite Candida albicans biofilm Candida krusei biofilm Cytocompatibility 

Notes

Acknowledgements

The authors are thankful to Fundação Fernando Pessoa for providing the facilities and financial support and to Fluidinova S.A. for the supply of NanoXIM. This research was also funded by FCT – Fundação para a Ciência e Tecnologia, through UID/MULTI/4546/2019 project, PhD grant SFRH/BD/72866/2010, Chemistry Research Centre of the University of Minho (UID/QUI/00686/2016 e UID/QUI/00686/2018), University of Minho, and Grant Nos. PTDC/SAU-BMA/111233/2009, whose financial support is acknowledged.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Neither human participants nor animals were used in this research.

References

  1. 1.
    Blankenship JR, Mitchell AP. How to build a biofilm: a fungal perspective. Curr Opin Microbiol. 2006;9(6):588–94.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Douglas LJ. Candida biofilms and their role in infection. Trends Microbiol. 2003;11(1):30–6.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Cauda R. Candidaemia in patients with an inserted medical device. Drugs. 2009;69(Suppl 1):33–8.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Cuéllar-Cruz M, Vega-González A, Mendoza-Novelo B, et al. The effect of biomaterials and antifungals on biofilm formation by Candida species: a review. Eur J Clin Microbiol. 2012;31(10):2513–27.CrossRefGoogle Scholar
  5. 5.
    Kuhn DM, Chandra J, Mukherjee PK, et al. Comparison of biofilms formed by Candida albicans and Candida parapsilosis on bioprosthetic surfaces. Infect Immun. 2002;70(2):878–88.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Silva S, Negri M, Henriques M, et al. Silicone colonization by non-Candida albicans Candida species in the presence of urine. J Med Microbiol. 2010;59(Pt 7):747–54.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Chandra J, Mukherjee PK, Leidich SD, et al. Antifungal resistance of Candida biofilms formed on denture acrylic in vitro. J Dent Res. 2001;80(3):903–8.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Ramage G, Martinez JP, Lopez-Ribot JL. Candida biofilms on implanted biomaterials: a clinically significant problem. FEMS Yeast Res. 2006;6(7):979–86.CrossRefGoogle Scholar
  9. 9.
    Hasan F, Xess I, Wang X, et al. Biofilm formation in clinical Candida isolates and its association with virulence. Microbes Infect. 2009;11(8–9):753–61.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Anagnostakos K, Kelm J, Schmitt E, et al. Fungal periprosthetic hip and knee joint infections clinical experience with a 2-stage treatment protocol. J Arthroplasty. 2012;27(2):293–8.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Azzam K, Parvizi J, Jungkind D, et al. Microbiological, clinical, and surgical features of fungal prosthetic joint infections: a multi-institutional experience. J Bone Joint Surg Am. 2009;91A:142–9.CrossRefGoogle Scholar
  12. 12.
    Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol. 2007;45(4):321–46.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Selmon GP, Slater RN, Shepperd JA, et al. Successful 1-stage exchange total knee arthroplasty for fungal infection. J Arthroplasty. 1998;13(1):114–5.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Parahitiyawa NB, Samaranayake YH, Samaranayake LP, et al. Interspecies variation in Candida biofilm formation studied using the Calgary biofilm device. APMIS. 2006;114(4):298–306.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Kojic EM, Darouiche RO. Candida infections of medical devices. Clin Microbiol Rev. 2004;17(2):255.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Junka AF, Szymczyk P, Smutnicka D, et al. Microbial biofilms are able to destroy hydroxyapatite in the absence of host immunity in vitro. J Oral Maxillofac Surg. 2015;73(3):451–64.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Ferraz MP, Monteiro FJ, Manuel CM. Hydroxyapatite nanoparticles: a review of preparation methodologies. J Appl Biomater Biomech. 2004;2(2):74–80.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Jimbo R, Coelho PG, Bryington M, et al. Nano hydroxyapatite-coated implants improve bone nanomechanical properties. J Dent Res. 2012;91(12):1172–7.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Venkatesan J, Kim SK. Nano-hydroxyapatite composite biomaterials for bone tissue engineering—a review. J Biomed Nanotechnol. 2014;10(10):3124–40.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Groza A, Ciobanu CS, Popa CL, et al. Structural properties and antifungal activity against Candida albicans biofilm of different composite layers based on Ag/Zn doped hydroxyapatite-polydimethylsiloxanes. Polymers. 2016.  https://doi.org/10.3390/polym8040131.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ciobanu CS, Groza A, Iconaru SL, et al. antimicrobial activity evaluation on silver doped hydroxyapatite/polydimethylsiloxane composite layer. Biomed Res Int. 2015;2015:926513.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Ciobanu CS, Iconaru SL, Chifiriuc MC, et al. Synthesis and antimicrobial activity of silver-doped hydroxyapatite nanoparticles. Biomed Res Int. 2013;2013:916218.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Erakovic S, Jankovic A, Ristoscu C, et al. Antifungal activity of Ag:hydroxyapatite thin films synthesized by pulsed laser deposition on Ti and Ti modified by TiO2 nanotubes substrates. Appl Surf Sci. 2014;293:37–45.CrossRefGoogle Scholar
  24. 24.
    Kathiravan MK, Salake AB, Chothe AS, et al. The biology and chemistry of antifungal agents: a review. Bioorg Med Chem. 2012;20(19):5678–98.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Cao X, Sun Z, Cao Y, et al. Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility. J Med Chem. 2014;57(9):3687–706.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Wisplinghoff H, Ebbers J, Geurtz L, et al. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. Int J Antimicrob Agents. 2014;43(1):78–81.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Ribeiro AI, Gabriel C, Cerqueira F, et al. Synthesis and antimicrobial activity of novel 5-aminoimidazole-4-carboxamidrazones. Bioorg Med Chem Lett. 2014;24(19):4699–702.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Barros J, Grenho L, Manuel C, et al. Influence of nanohydroxyapatite surface properties on Staphylococcus epidermidis biofilm formation. J Biomater Appl. 2014;28(9):1325–35.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Grenho L, Monteiro FJ, Pia Ferraz M. In vitro analysis of the antibacterial effect of nanohydroxyapatite-ZnO composites. J Biomed Mater Res A. 2014;102(10):3726–33.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Bachmann SP, VandeWalle K, Ramage G, et al. In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother. 2002;46(11):3591–6.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Balestrino D, Souweine B, Charbonnel N, et al. Eradication of microorganisms embedded in biofilm by an ethanol-based catheter lock solution. Nephrol Dial Transpl. 2009;24(10):3204–9.CrossRefGoogle Scholar
  32. 32.
    Pfaller MA, Diekema DJ, Gibbs DL, et al. Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. J Clin Microbiol. 2008;46(2):515–21.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Tumbarello M, Posteraro B, Trecarichi EM, et al. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J Clin Microbiol. 2007;45(6):1843–50.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Rex JH, Walsh TJ, Sobel JD, et al. Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. Clin Infect Dis. 2000;30(4):662–78.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Seneviratne CJ, Jin L, Samaranayake LP. Biofilm lifestyle of Candida: a mini review. Oral Dis. 2008;14(7):582–90.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Inigo M, Peman J, Del Pozo JL. Antifungal activity against Candida biofilms. Int J Artif Organs. 2012;35(10):780–91.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Yoshijima Y, Murakami K, Kayama S, et al. Effect of substrate surface hydrophobicity on the adherence of yeast and hyphal Candida. Mycoses. 2010;53(3):221–6.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Samaranayake YH, Wu PC, Samaranayake LP, et al. Relationship between the cell surface hydrophobicity and adherence of Candida krusei and Candida albicans to epithelial and denture acrylic surfaces. APMIS. 1995;103(10):707–13.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Frade JP, Arthington-Skaggs BA. Effect of serum and surface characteristics on Candida albicans biofilm formation. Mycoses. 2010;54(4):e154–62.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol. 2001;183(18):5385–94.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Lopez-Ribot JL. Candida albicans biofilms: more than filamentation. Curr Biol. 2005;15(12):R453–5.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Sudbery P, Gow N, Berman J. The distinct morphogenic states of Candida albicans. Trends Microbiol. 2004;12(7):317–24.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Ma SL, Li H, Yan C, et al. Antagonistic effect of protein extracts from Streptococcus sanguinis on pathogenic bacteria and fungi of the oral cavity. Exp Ther Med. 2014;7(6):1486–94.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • C. Gabriel
    • 1
  • L. Grenho
    • 1
    • 2
    • 3
    • 4
    • 5
    • 9
    Email author
  • F. Cerqueira
    • 1
    • 6
  • R. Medeiros
    • 1
    • 6
    • 7
  • A. M. Dias
    • 8
  • A. I. Ribeiro
    • 8
  • M. F. Proença
    • 8
  • M. H. Fernandes
    • 5
    • 9
  • J. C. Sousa
    • 1
  • F. J. Monteiro
    • 2
    • 3
    • 4
  • M. P. Ferraz
    • 1
    • 2
    • 3
    • 6
  1. 1.Health Sciences FacultyUniversity Fernando PessoaPortoPortugal
  2. 2.i3S - Instituto de Investigação e Inovação em SaúdeU. PortoPortoPortugal
  3. 3.INEB - Instituto de Engenharia BiomédicaU. PortoPortoPortugal
  4. 4.Departamento de Engenharia Metalúrgica e Materiais, Faculdade de EngenhariaU. PortoPortoPortugal
  5. 5.Laboratory for Bone Metabolism and Regeneration, Faculty of Dental MedicineU. PortoPortoPortugal
  6. 6.FP-ENAS/CEBIMED, Energy, Environment and Health Research Unit/Biomedical Research CenterUniversity Fernando PessoaPortoPortugal
  7. 7.Molecular Oncology GRP and Molecular Biology Laboratory - Virology ServicePortuguese Institute of Oncology (IPO)PortoPortugal
  8. 8.Department of Chemistry, Centre of ChemistryUniversity of MinhoBragaPortugal
  9. 9.REQUIMTE/LAQVU. PortoPortoPortugal

Personalised recommendations