Antifungal activity of polyphenolic compounds against fluconazole-susceptible and -resistant Candida species
-
Harmed Fakhim
,
Bahar Mohamadi
,
Shima Gharibi
,
Medhi Rahimmalek
,
Mahnaz Hosseini Rizi
,
Mahsa Shelerangkon
,
Elahe Nasri
,
Fariba Dorostkar
,
Antoni Szumny
,
Afsane Vaezi
Abstract
Background and Objectives: The rapid emergence of resistant fungi is occurring worldwide, and this crisis has been attributed to the lack of new antifungal drug development. This issue emphasizes the need for innovation in finding novel antifungals. There is an increasing interest in using the natural products of plants with high biological activity as alternatives to synthetic drugs. This study aimed to evaluate the possible applicability of polyphenols as alternative antifungal drugs to treat resistant Candida infections.
Materials and Methods: A panel of fluconazole-resistant (n=14) and fluconazole-susceptible (n=26) clinical Candida isolates was obtained from the reference culture collection. The determination of the minimum inhibitory concentrations (MICs) of fluconazole, tannic acid, rosmarinic acid, gallic acid, chlorogenic acid, caffeic, ferulic, and p-coumaric was carried out following the Clinical and Laboratory Standards Institute (CLSI) guidelines.
Results: The MIC values of 40 Candida species isolates ranged from 0.25 to >64 µg/mL for polyphenolic compounds. The highest inhibitory effect against Candida species was observed with tannic acid, followed by fluconazole. Non-albicans Candida groups were more sensitive to tannic acid compared to C. albicans isolates. Significant differences were observed in the MICs of fluconazole and tannic acid against non-albicans Candida isolates.
Conclusion: The increasing antifungal resistance highlights the importance of evaluating new drugs that are more robust against resistance. This study suggests that tannic acid could be considered a novel antifungal agent for managing fungal infections, including multidrug-resistant non-albicans Candida infections.
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23. Nasri E, Vaezi A, Falahatinejad M, Rizi MH, Sharifi M, Sadeghi S, et al. Species distribution and susceptibility profiles of oral candidiasis in hematological malignancy and solid tumor patients. Braz J Microbiol 2023; 54: 143-149.
24. Nasri E, Fakhim H, Vaezi A, Khalilzadeh S, Ahangarkani F, Laal kargar M, et al. Airway colonisation by Candida and Aspergillus species in Iranian cystic fibrosis patients. Mycoses 2019; 62: 434-440.
25. Clinical and Laboratory Standards Institute (CLSI) (2017). Performance Standards for Antifungal Susceptibility Testing of Yeasts. 1st ed. CLSI supplement M60. https://clsi.org/media/1895/m60ed1_sample.pdf
26. Hodaei M, Rahimmalek M, Arzani A. Variation in bioactive compounds, antioxidant and antibacterial activity of Iranian Chrysanthemum morifolium cultivars and determination of major polyphenolic compounds based on HPLC analysis. J Food Sci Technol 2021; 58: 1538-1548.
27. Evensen NA, Braun PC. The effects of tea polyphenols on Candida albicans: inhibition of biofilm formation and proteasome inactivation. Can J Microbiol 2009; 55: 1033-1039.
28. Sung WS, Lee DG. Antifungal action of chlorogenic acid against pathogenic fungi, mediated by membrane disruption. Pure Appl Chem 2010; 82: 219-226.
29. Ma CM, Abe T, Komiyama T, Wang W, Hattori M, Daneshtalab M. Synthesis, anti-fungal and 1, 3-β-d-glucan synthase inhibitory activities of caffeic and quinic acid derivatives. Bioorg Med Chem 2010; 18: 7009-7014.
30. Ahmad A, Khan A, Manzoor N. Reversal of efflux mediated antifungal resistance underlies synergistic activity of two monoterpenes with fluconazole. Eur J Pharm Sci 2013; 48: 80-86.
31. Khan MS, Ahmad I. Antibiofilm activity of certain phytocompounds and their synergy with fluconazole against Candida albicans biofilms. J Antimicrob Chemother 2012; 67: 618-621.
32. Zore GB, Thakre AD, Jadhav S, Karuppayil SM. Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle. Phytomedicine 2011; 18: 1181-1190.
33. Huang S, Cao YY, Dai BD, Sun XR, Zhu ZY, Cao YB, et al. In vitro synergism of fluconazole and baicalein against clinical isolates of Candida albicans resistant to fluconazole. Biol Pharm Bull 2008; 31: 2234-2236.
2. Perlin DS. Antifungal drug resistance: do molecular methods provide a way forward? Curr Opin Infect Dis 2009; 22: 568-573.
3. Sanyaolu A, Okorie C, Marinkovic A, Abbasi AF, Prakash S, Mangat J, et al. Candida auris: an overview of the emerging drug-resistant fungal infection. Infect Chemother 2022; 54: 236-246.
4. Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 2012; 125(1 Suppl): S3-S13.
5. Hashemi SE, Shokohi T, Abastabar M, Aslani N, Ghadamzadeh M, Haghani I. Species distribution and susceptibility profiles of Candida species isolated from vulvovaginal candidiasis, emergence of C. lusitaniae. Curr Med Mycol 2019; 5: 26-34.
6. Davari A, Hedayati MT, Jafarzadeh J, Nikmanesh B, Nabili M, Hamidieh AA, et al. Evaluation of Candida colonization index, molecular identification, and antifungal susceptibility pattern of Candida species isolated from critically ill pediatric patients: A singlecenter study in Iran. Curr Med Mycol 2022; 8: 15-21.
7. Banerjee S, Denning DW, Chakrabarti A. One Health aspects & priority roadmap for fungal diseases: A mini-review. Indian J Med Res 2021; 153: 311-319.
8. Sadeghi-Ghadi Z, Vaezi A, Ahangarkani F, Ilkit M, Ebrahimnejad P, Badali H. Potent in vitro activity of curcumin and quercetin co-encapsulated in nanovesicles without hyaluronan against Aspergillus and Candida isolates. J Mycol Med 2020; 30: 101014.
9. CDC (2019). Prevention. Antibiotic resistance threats in the United States. US Department of Health and Human Services, Centres for Disease Control Prevention. https://ndc.services.cdc.gov/wp-content/uploads/Antibiotic-Resistance-Threats-in-the-United-States-2019.pdf
10. Beardsley J, Halliday CL, Chen SC, Sorrell TC. Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside. Future Microbiol 2018; 13: 1175-1191.
11. Sanglard D. Emerging threats in antifungal-resistant fungal pathogens. Front Med (Lausanne) 2016; 3: 11.
12. Vaezi A, Fakhim H, Javidnia J, Khodavaisy S, Abtahian Z, Vojoodi M, et al. Pesticide behavior in paddy fields and development of azole-resistant Aspergillus fumigatus: should we be concerned? J Mycol Med 2018; 28: 59-64.
13. Daglia M. Polyphenols as antimicrobial agents. Curr Opin Biotechnol 2012; 23: 174-181.
14. Fraga CG, Croft KD, Kennedy DO, Tomás-Barberán FA. The effects of polyphenols and other bioactives on human health. Food Funct 2019; 10: 514-528.
15. Bouarab Chibane L, Degraeve P, Ferhout H, Bouajila J, Oulahal N. Plant antimicrobial polyphenols as potential natural food preservatives. J Sci Food Agric 2019; 99: 1457-1474.
16. Efenberger-Szmechtyk M, Nowak A, Czyzowska A. Plant extracts rich in polyphenols: Antibacterial agents and natural preservatives for meat and meat products. Crit Rev Food Sci Nutr 2021; 61: 149-178.
17. Olszewska MA, Gedas A, Simões M. Antimicrobial polyphenol-rich extracts: Applications and limitations in the food industry. Food Res Int 2020; 134: 109214.
18. Skroza D, Šimat V, Smole Možina S, Katalini´c V, Boban N, Generali´c Mekini´c I. Interactions of resveratrol with other phenolics and activity against food-borne pathogens. Food Sci Nutr 2019; 7: 2312-2318.
19. Diba K, Makhdoomi K, Nasri E, Vaezi A, Javidnia J, Gharabagh DJ, et al. Emerging Candida species isolated from renal transplant recipients: species distribution and susceptibility profiles. Microb Pathog 2018; 125: 240-245.
20. Fakhim H, Chowdhary A, Prakash A, Vaezi A, Dannaoui E, Meis JF, et al. In vitro interactions of echinocandins with triazoles against multidrug-resistant Candida auris. Antimicrob Agents Chemother 2017; 61(11): e01056-17.
21. Fakhim H, Emami S, Vaezi A, Hashemi SM, Faeli L, Diba K, et al. In vitro activities of novel azole compounds ATTAF-1 and ATTAF-2 against fluconazole-susceptible and-resistant isolates of Candida species. Antimicrob Agents Chemother 2016; 61(1): e01106-16.
22. Fakhim H, Vaezi A, Javidnia J, Nasri E, Mahdi D, Diba K, et al. Candida africana vulvovaginitis: Prevalence and geographical distribution. J Mycol Med 2020; 30: 100966.
23. Nasri E, Vaezi A, Falahatinejad M, Rizi MH, Sharifi M, Sadeghi S, et al. Species distribution and susceptibility profiles of oral candidiasis in hematological malignancy and solid tumor patients. Braz J Microbiol 2023; 54: 143-149.
24. Nasri E, Fakhim H, Vaezi A, Khalilzadeh S, Ahangarkani F, Laal kargar M, et al. Airway colonisation by Candida and Aspergillus species in Iranian cystic fibrosis patients. Mycoses 2019; 62: 434-440.
25. Clinical and Laboratory Standards Institute (CLSI) (2017). Performance Standards for Antifungal Susceptibility Testing of Yeasts. 1st ed. CLSI supplement M60. https://clsi.org/media/1895/m60ed1_sample.pdf
26. Hodaei M, Rahimmalek M, Arzani A. Variation in bioactive compounds, antioxidant and antibacterial activity of Iranian Chrysanthemum morifolium cultivars and determination of major polyphenolic compounds based on HPLC analysis. J Food Sci Technol 2021; 58: 1538-1548.
27. Evensen NA, Braun PC. The effects of tea polyphenols on Candida albicans: inhibition of biofilm formation and proteasome inactivation. Can J Microbiol 2009; 55: 1033-1039.
28. Sung WS, Lee DG. Antifungal action of chlorogenic acid against pathogenic fungi, mediated by membrane disruption. Pure Appl Chem 2010; 82: 219-226.
29. Ma CM, Abe T, Komiyama T, Wang W, Hattori M, Daneshtalab M. Synthesis, anti-fungal and 1, 3-β-d-glucan synthase inhibitory activities of caffeic and quinic acid derivatives. Bioorg Med Chem 2010; 18: 7009-7014.
30. Ahmad A, Khan A, Manzoor N. Reversal of efflux mediated antifungal resistance underlies synergistic activity of two monoterpenes with fluconazole. Eur J Pharm Sci 2013; 48: 80-86.
31. Khan MS, Ahmad I. Antibiofilm activity of certain phytocompounds and their synergy with fluconazole against Candida albicans biofilms. J Antimicrob Chemother 2012; 67: 618-621.
32. Zore GB, Thakre AD, Jadhav S, Karuppayil SM. Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle. Phytomedicine 2011; 18: 1181-1190.
33. Huang S, Cao YY, Dai BD, Sun XR, Zhu ZY, Cao YB, et al. In vitro synergism of fluconazole and baicalein against clinical isolates of Candida albicans resistant to fluconazole. Biol Pharm Bull 2008; 31: 2234-2236.
| Files | ||
| Issue | Vol 17 No 2 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i2.18398 | |
| Keywords | ||
| Tannic acid; Polyphenolic compounds; Candida species; Fluconazole resistance; Antifungal activity | ||
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How to Cite
1.
Fakhim H, Mohamadi B, Gharibi S, Rahimmalek M, Hosseini Rizi M, Shelerangkon M, Nasri E, Dorostkar F, Szumny A, Vaezi A. Antifungal activity of polyphenolic compounds against fluconazole-susceptible and -resistant Candida species. Iran J Microbiol. 2025;17(2):342-347.
