Hrynzovska А. А., Bobyr V. V.
STUDY OF THE SENSITIVITY OF CANDIDA ADAPTED TO FUNGICIDES TO MEDICAL ANTIFUNGAL DRUGS
Show/Download
About the author:
Hrynzovska А. А., Bobyr V. V.
Heading:
MICROBIOLOGY
Type of article:
Scientific article
Annotation:
Nowadays, fungal resistance to antifungal drugs is one of the most pressing problems in modern medicine and is subject to in-depth study. It is possible that this may also be due to the fact that antimycotic drugs, in addition to the medical industry, are widely used in various sectors of the national economy, including the agricultural industry, where fungicidal drugs of the azole group, in particular triazole and imidazole derivatives, are most often used. This study aims to assess how the adaptation of microscopic fungi to azole fungicides affects their sensitivity to drugs used in the medical field to treat fungal infections. It is known that antifungal drugs from the class of imidazoles and triazoles, both medical and non-medical, have the same mechanism of action on fungal cells. In addition, the comparative analysis showed significant structural similarities between fragments of pesticide (fungicide) molecules and antifungal drugs, which justifies the choice of similarly structured compounds from these classes for the study. Based on the above criteria, fungicides and drugs of similar structure from both the triazole and imidazole classes were selected for the study. The results show that C. albicans strain 1, adapted to high concentrations of tebuconazole fungicide, showed increased susceptibility to nystatin, imidazoles (miconazole and clotrimazole) and fluconazole. All strains adapted to high doses of fungicides developed sensitivity to fluconazole, but strains adapted to triazole fungicides (difenoconazole and propiconazole) lost sensitivity to voriconazole, indicating the formation of cross-resistance. At the same time, it was found that C. glabrata 91 strains resistant to the fungicide difenoconazole were able to retain sensitivity to triazole drugs when analysing the results after 24 hours, but after 48 hours the growth retardation zone was completely “overgrown”, which may indicate the formation of cross-resistance in a slow-growing population. Based on the data obtained, it can be reasonably concluded that fungal strains adapted to high concentrations of fungicides can develop cross-resistance to medical antimycotics, especially to drugs with a similar chemical structure. However, in some cases, on the contrary, there is an increase in sensitivity to medical antifungal drugs.
Tags:
Bibliography:
- Prakash H, Chakrabarti A. Global Epidemiology of Mucormycosis. J Fungi (Basel). 2019;5(1):26. DOI: 10.3390/jof5010026.
- Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015;40(4):277-83.
- Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ. Emerging fungal threats to animal, plant and ecosystem health. Nature. 2012;484(7393):186-94. DOI: 10.1038/nature10947.
- Kunova A, Pizzatti C, Saracchi M, Pasquali M, Cortesi P. Grapevine Powdery Mildew: Fungicides for Its Management and Advances in Molecular Detection of Markers Associated with Resistance. Microorganisms. 2021;9(7):1541. DOI: 10.3390/microorganisms9071541.
- Fisher MC, Hawkins NJ, Sanglard D, Gurr SJ. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science. 2018;360(6390):739-742. DOI: 10.1126/science.aap7999.
- Lucas JA, Hawkins NJ, Fraaije BA. The evolution of fungicide resistance. Adv Appl Microbiol. 2015;90:29-92. DOI: 10.1016/bs.aambs.2014.09.001.
- Chowdhary A, Sharma C, Meis JF. Azole-Resistant Aspergillosis: Epidemiology, Molecular Mechanisms, and Treatment. J Infect Dis. 2017;216(3):S436-S444. DOI: 10.1093/infdis/jix210.
- MOZ Ukrayiny. Metodychni rekomendatsiyi «Vyvchennya spetsyfichnoyi aktyvnosti antyfunhalʹnykh likarsʹkykh zasobiv». Kyyiv: Ministerstvo okhorony zdorovʺya Ukrayiny, DP «Derzhavnyy ekspertnyy tsentr MOZ Ukrayiny»; 2016. 60 s. [in Ukrainian].
- CLSI. Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts. 3rd ed. CLSI guideline M44. Wayne: Clinical and Laboratory Standards Institute; 2018.
- Hrynzovska AA, Bobyr VV. The formation of mechanisms of cross-resistance of A. fumigatus due to the chemical similarity of azole antifungals and fungicides. Nation’s Health. 2023;3:27-33. DOI: 10.32782/2077-6594/2023.3/04.
Publication of the article:
«Bulletin of problems biology and medicine», 2024 Issue 2, 173, 348-357 pages, index UDC 615.282.015.8:579.61
