Iungin O. S.


About the author:

Iungin O. S.



Type of article:

Scentific article


As long as in Ukraine and all over the world Candida spp. causes dangerous mycosis in immunosuppressive patients new drugs and targets for antifungal treatment needs to be found. In this review it is analysed available antifungal agents used to treat diseases caused by Candida spp. including resistant to azoles drugs C. albicans and non-albicans species. It was also estimated the ratio of C. albicans and non-albicans species in causing hospital infections. It was shown the ability of hospital C. albicans and non-albicans species to form biofilms as well. Different classes of drugs are described by the targets of their action focused on cell compartments. Among them are echinocandins, polyenes antibiotics, pyrimidines etc. These groups have been shown as the most effective against azole-resistant Candida strains. Also, the phenomenon of biofilm formation in the pathogenesis of mycoses were described as well as new targets for antifungal drugs associated with the formation of biofilms: quorum-sensing molecules, exopolymer matrix, eDNA. These new targets are the promising way for resistant species treatment. The effective way to combat hard infection is to combine antibiofilm and antifungal treatment to make described drugs work. Particular attention is focused on drugs that can suppress the formation of biofilms. Antimicrobial compounds binding with DNA/RNA used as new anti-biofilm drugs. The most effective representatives of this group are diamidines and flucytosine. Fungal quorum-sensing molecules (farnesol and tirosol) could be the potential targets for drug development as these molecules were described as virulent agents and coordinates yeast-host relations. As another effective approach to improve the tactics of antifungal treatment, a comprehensive use of drugs with a synergistic mechanism of action is considered.


antifungal agents, biofilm, C. albicans, resistance


  1. Dühring S, Germerodt S, Skerka C, Zipfel PF, Dandekar T, Schuster S. Host-pathogen interactions between the human innate immune system and Candida albicans – understanding and modeling defense and evasion strategies. Frontiers in microbiology. 2015;6:618-25.
  2. Tumbarello M, Posteraro B, Trecarichi E, Fiori B, Rossi M, Porta R, et al. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. Journal of clinical microbiology. 2007;45(6):1843-50.
  3. Holubka OV. Poshyrenist kandydoziv, zahalna kharakterystyka zbudnyka, osoblyvosti laboratornoi diahnostyk. Annaly Mechnykovskoho instytutu. 2011;2:51-9. [in Ukrainian].
  4. Bossche HV. Anti-Candida Drugs – Mechanisms of Action. Candida and Candidamycosis. Springer, Boston, MA; 1991. р. 83-95.
  5. Vanden Bossche H, Marichal P, Odds F. Molecular mechanisms of drug resistance in fungi. Trends Microbiol. 1994;2:393-400.
  6. Sardi J, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJS. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. Journal of medical microbiology. 2013;62(1):10-24.
  7. Nett JE, Sanchez H, Cain MT, Andes DR. Genetic basis of Candida biofilm resistance due to drug-sequestering matrix glucan. The Journal of infectious diseases. 2010;202(1):171-5.
  8. Taff HT, Nett JE, Zarnowski R, Ross KM, Sanchez H, Cain MT, et al. A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS pathogens. 2012;8(8):e1002848.
  9. Gow NAR, Brown AJP, Odds FC. Fungal morphogenesis and host invasion. Current opinion in microbiology. 2002;5(4):366-71.
  10. Machida K, Tanaka T, Yano Y, Otani S, Taniguchi M. Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism. Microbiology. 1999;145(2):293-9.
  11. Leonhardt I, Spielberga S, Webera M, Albrecht-Eckardtb D, Blässc M, Clausc R, et al. The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity. MBio. 2015;6(2):e00143-15.
  12. Albuquerque P, Casadevall A. Quorum sensing in fungi – a review. Medical mycology. 2012;50(40):337-45.
  13. Vlasenko IO, Aram D, Davtian LL. Vyvchennia asortymentu likarskykh zasobiv dlia mistsevoho likuvannia hrybkovykh urazhen, shcho uskladneni keratozom. Farmatsevtychnyi zhurnal. 2013;6:15. [in Ukrainian].
  14. Kyrychek LT. Antybyotyky v sovremennoi khymyoterapyy. Mezhdunarodnyi medytsynskyi zhurnal. 2003;1:118-21. [in Russiаn].
  15. De Beule K, Van Gestel J. Pharmacology of itraconazole. Drugs. 2001;61(1):27-37.
  16. Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrobial agents and chemotherapy.1995;39(1):1-12.
  17. Paczkowska I, Wójtowicz A, Malm A. Wybrane aspekty farmakoterapii kandydoz. Ter Leki. 2010;66:539-43.
  18. Arendrup MC, Patterson TF. Multidrug-resistant Candida: epidemiology, molecular mechanisms, and treatment. The Journal of infectious diseases. 2017;216(3):445-51.
  19. Gauthier GM, Nork TM, Prince R, Andes D. Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis. Clinical Infectious Diseases. 2005;41(3):27-8.
  20. Nett J, Lincoln L, Marchillo K, Massey R, Holoyda K, Hoff B, et al. Putative role of β-1, 3 glucans in Candida albicans biofilm resistance. Antimicrobial agents and chemotherapy. 2007;51(2):510-20.
  21. Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrobial agents and chemotherapy. 2002;46(6):1773-80.
  22. Uppuluri P, Nett J, Heitman J, Andes D. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms. Antimicrobial agents and chemotherapy. 2008;52(3):1127-32.
  23. Martins M, Uppuluri P, Thomas DP, Cleary IA, Henriques M, Lopez-Ribot JL, et al. Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms. Mycopathologia. 2010;169(5):323-31.
  24. Spampinato C, Leonardi D. Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. BioMed research international. 2013;20:13-25.
  25. Nguyen ST, Kwasny SM, Ding X, Williams JD, Peet NP, Bowlin TL, et al. Synthesis and antifungal evaluation of head-to-head and head-to-tail bisamidine compounds. Bioorganic & medicinal chemistry. 2015;23(17):5789-98.
  26. Shrestha SK, Kril LM, Green KD, Kwiatkowski S, Sviripa VM, Nickell JR, et al. Bis (N-amidinohydrazones) and N-(amidino)-N′-aryl-bishydrazones: new classes of antibacterial/antifungal agents. Bioorganic & medicinal chemistry. 2017;25(1):58-66.
  27. Koliadenko VH, Korolenko VV, Bondur VV. Protyhrybkovi zasoby: suchasne ta maibutnie. Ukr. zhurn. dermatol., venerol., kosmetol. 2004;3:14. [in Ukrainiаn].

Publication of the article:

«Bulletin of problems biology and medicine» Issue 2 (144), 2018 year, 83-86 pages, index UDK 579.6