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BioNanoScience

, Volume 9, Issue 3, pp 539–544 | Cite as

Development of Novel Effective Agents Against Candida albicans Biofilms

  • Liliya E. NikitinaEmail author
  • Svetlana А. Lisovskaya
  • Valeriya A. Startseva
  • Roman S. Pavelyev
  • Ilmir R. Gilfanov
  • Inna V. Fedyunina
  • Olga V. Ostolopovskaya
  • Rustem F. Akhverdiev
Article
  • 49 Downloads

Abstract

It is common knowledge that Candida albicans are one of the main sources of fungal infections which may lead to inflammation or even threaten life. Until now, fungal infection treatment has been considered as a challenging task due to several problems associated with their application like toxicity, drug interactions, and resistance. This paper outlines a new approach to develop effective agents against Candida albicans biofilms. The impact of borneols and sulfur-containing terpenoids of bornane series on the in vitro formation and growth of clinical strain of C. albicans in biofilms has been studied and compared with modern antimycotics. As a result, thioterpenoid 4 minimum inhibitory concentrations for C. albicans strain plankton ranged from 100 to 200 μg/ml where biofilm growth inhibition occurred at the concentration of 200 μg/ml. It is generally accepted that fluconazole 7 is widely used in clinical practice but still not effective against biofilms of C. albicans fungi. Therefore, we believe that isoborneol 2 and thioterpenoids 3 and 4, as well as terbinafine 6, can be promising starting points for the development of new antifungal agents against the pathogenic activity of fungi including pathogens embedded in biofilms since they demonstrated an effective resistance against the formation of pseudomycelia.

Keywords

Candida albicans Biofilms Antifungal activity Monoterpenoids 

Notes

Compliance with Ethical Standards

Conflict of Interest

None.

Research Involving Humans and Animals Statement

None.

Informed Consent

None.

Funding Statement

None.

References

  1. 1.
    Hung, C., Kao, K., Wang, N., Hu, C., Hsieh, J., & Fu, Y. (2012). Invasive fungal infection among hematopoietic stem cell transplantation patients with mechanical ventilation in the intensive care unit. BMC Infectious Diseases, 10, 1186–1471.Google Scholar
  2. 2.
    Pinner, R. W. (1996). Trends in infectious diseases mortality in the United States. Journal of the American Medical Association, 275(3), 189–193.CrossRefGoogle Scholar
  3. 3.
    Brown, G. D., Denning, D. W., & Gow, N. A. (2012). Hidden killers: human fungal infections. Science Translational Medicine, 19(4), 165rv13.Google Scholar
  4. 4.
    Murray, C. J., Rosenfeld, L. C., & Lim, S. S. (2012). Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet, 4(379), 413–431.CrossRefGoogle Scholar
  5. 5.
    Morio, F. (2010). Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature. Diagnostic Microbiology and Infectious Disease, 66(4), 373–384.CrossRefGoogle Scholar
  6. 6.
    Xiang, M. J., Liu, J. Y., Wang, S., & Shi, C. (2013). Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans. FEMS Yeast Research, 13(4), 386–393.CrossRefGoogle Scholar
  7. 7.
    Nikitina, L. E., Startseva, V. A., Vakulenko, I. A., Khismatulina, I. M., Lisovskaya, S. A., Glushko, N. P., & Fassakhov, R. S. (2009). Synthesis and antifungal activity of compounds of the pinane series. Pharmaceutical Chemistry Journal, 43(5), 251–254.CrossRefGoogle Scholar
  8. 8.
    Gavrilov, V. V., Startseva, V. A., Nikitina, L. E., Lodochnikova, O. A., Gnezdilov, O. I., Lisovskaya, S. A., Glushko, N. I., & Klimovitskii, E. N. (2010). Synthesis and antifungal activity of sulfides, sulfoxides, and sulfones based on (1S)-(-)-β-pinene. Pharmaceutical Chemistry Journal, 44(3), 126–129.CrossRefGoogle Scholar
  9. 9.
    Nikitina, L. E., Startseva, V. A., Dorofeeva, L. Y., Artemova, N. P., Kuznetsov, I. V., Lisovskaya, S. A., & Glushko, N. P. (2010). Antifungal activity of bicyclic monoterpenoids and terpenesulfides. Chemistry of Natural Compounds, 46(1), 28–32.CrossRefGoogle Scholar
  10. 10.
    Nikitina, L. E., Startseva, V. A., Artemova, N. P., Dorofeeva, L. Y., Kuznetsov, I. V., Lisovskaya, S. A., Glushko, N. P., & Kutyreva, M. P. (2012). Synthesis and antifungal activity of monoterpenoids of the carane series. Pharmaceutical Chemistry Journal, 45(11), 664–667.CrossRefGoogle Scholar
  11. 11.
    Nikitina, L. E., Artemova, N. P., Startseva, V. A., Fedyunina, I. V., & Klochkov, V. V. (2017). Biological activity of S-containing monoterpenoids. Chemistry of Natural Compounds, 53(5), 811–819.CrossRefGoogle Scholar
  12. 12.
    European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Dieases (ESCMID). EUCAST Definitive Document E.DEF 1.2. (2000). Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by agar dilution. Clinical Microbiology and Infection, 6(9), 503–508.CrossRefGoogle Scholar
  13. 13.
    Ishmuratov, G. Y., Yakovleva, M. P., Tukhvatshin, V. S., Talipov, R. F., Nikitina, L. E., Artemova, N. P., Startseva, V. A., & Tolstikov, G. A. (2014). Sulfurcontaining derivatives of mono- and bicyclic natural monoterpenoids. Chemistry of Natural Compounds, 50(1), 22–47.CrossRefGoogle Scholar
  14. 14.
    Leclercq, R., Canto’n, R., Brown, D. F. J., Giske, C. G., Heisig, P., MacGowan, A. P., Mouton, J. W., Nordmann, P., Rodloff, A. C., Rossolini, G. M., Soussy, C.-J., Steinbakk, M., Winstanley, T. G., & Kahlmeter, G. (2013). EUCAST expert rules in antimicrobial susceptibility testing. Clinical Microbiology and Infection, 19(2), 141–160.CrossRefGoogle Scholar
  15. 15.
    Ramage, G., Walle, K. V., Wickes, B. L., & Lopez-Ribot, J. L. (2001). Standartized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrobial Agents and Chemotherapy, 45, 2475–2479.CrossRefGoogle Scholar
  16. 16.
    Herigstad, B., Hamilton, M., & Heersink, J. (2001). How to optimize the drop plate method for enumerating bacteria. Journal of Microbiological Methods, 44(2), 121–129.CrossRefGoogle Scholar
  17. 17.
    Peeters, E., Nelis, H. J., & Coenye, T. (2008). Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates. Journal of Microbiological Methods, 72(2), 157–165.CrossRefGoogle Scholar
  18. 18.
    Kumari, V., Banerjee, T., Kumar, P., Pandey, S., & Tilak, R. (2013). Emergence of nonalbicans Candida among candidal vulvovaginitis cases and study of their potential virulence factors, from a tertiary care center, North India. Indian Journal of Pathology & Microbiology, 56, 144–147.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Liliya E. Nikitina
    • 1
    • 2
    Email author
  • Svetlana А. Lisovskaya
    • 1
    • 3
  • Valeriya A. Startseva
    • 1
    • 2
  • Roman S. Pavelyev
    • 2
  • Ilmir R. Gilfanov
    • 1
  • Inna V. Fedyunina
    • 1
  • Olga V. Ostolopovskaya
    • 2
    • 4
  • Rustem F. Akhverdiev
    • 5
  1. 1.Kazan State Medical UniversityKazanRussian Federation
  2. 2.Kazan (Volga Region) Federal UniversityKazanRussian Federation
  3. 3.Scientific Research Institute of Epidemiology and MicrobiologyKazanRussian Federation
  4. 4.Kazan State Medical AcademyKazanRussian Federation
  5. 5.Kazan National Research Technological UniversityKazanRussian Federation

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