Impact of oleuropein on Candida albicans and Staphylococcus aureus adhesion and its mediated toxicity in Zebrafish (Danio rerio) embryos
-
Samira Karzani
,
Aghil Sharifzadeh
,
Bahar Nayeri-Fasaei
,
Ali Reza Khosravi
,
Jalal Hassan
,
Aram Sharifi
,
Ali Pourshaban Shahrestani
Abstract
Background and Objectives: The rising prevalence of antibiotic resistance and biofilm-associated infections poses significant challenges in clinical settings. This study investigates the antimicrobial and anti-adhesive properties of oleuropein, a compound derived from olive leaves, against Candida albicans and Staphylococcus aureus.
Materials and Methods: This study was conducted on Candida albicans (fluconazole-resistant/susceptible) and Staphylococcus aureus (methicillin-resistant/susceptible). The antifungal, antibacterial, anti-adhesion, and cell surface hydrophobicity (CSH) effects of oleuropein were evaluated. The impact of oleuropein on germ tube formation (GTF) in C. albicans was assessed. Finally, the toxicity of oleuropein was evaluated in zebrafish embryos.
Results: Oleuropein exhibited MIC values of 10 mg/ml for C. albicans and 5 mg/ml for S. aureus. It significantly (P< 0.05) reduced the adhesion of both microorganisms in a dose-dependent manner, with inhibition percentages of 78.43% and 75.91% for C. albicans and S. aureus, respectively. Additionally, oleuropein reduced the CSH of C. albicans, indicating its potential to interfere with adhesion mechanisms. In addition, oleuropein exhibited inhibition of GTF in C. albicans.
Conclusion: Oleuropein demonstrates significant antimicrobial and anti-adhesive properties against C. albicans and S. aureus, indicating its potential as a therapeutic agent for preventing biofilm-related infections. However, careful dosage management is crucial due to its observed toxicity at higher concentrations.
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11. Ahamad J, Toufeeq I, Khan MA, Ameen MSM, Anwer ET, Uthirapathy S, et al. Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome. Phytother Res 2019; 33: 3112-3128.
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14. Vijakumaran U, Goh N-Y, Razali RA, Abdullah NAH, Yazid MD, Sulaiman N. Role of olive bioactive compounds in respiratory diseases. Antioxidants (Basel) 2023; 12: 1140.
15. Hassan J, Koohi MK, Sharifzadeh A, Babaei M, Moghadam S, Pourshaban Sharestani A. Extraction and purification of oleuropein from olive leaves. Nat Prod Res 2024; 1-9.
16. CLSI (2021). Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI supplement M100. Clinical and Laboratory Standards Institute.
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18. Danchik C, Casadevall A. Role of cell surface hydrophobicity in the pathogenesis of medically-significant fungi. Front Cell Infect Microbiol 2021; 10: 594973.
19. Camaioni L, Ustyanowski B, Buisine M, Lambert D, Sendid B, Billamboz M, et al. Natural compounds with antifungal properties against Candida albicans and Identification of Hinokitiol as a promising antifungal drug. Antibiotics (Basel) 2023; 12: 1603.
20. Sobanska M, Scholz S, Nyman A-M, Cesnaitis R, Gutierrez Alonso S, Klüver N, et al. Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH). Environ Toxicol Chem 2018; 37: 657-670.
21. Xu S, Chen F, Zhang H, Huang Z-l, Li J, Wu D, et al. Development a high-throughput zebrafish embryo acute toxicity testing method based on OECD TG 236. Toxicol Mech Methods 2023; 33: 104-112.
22. Mourer T, El Ghalid M, Pehau-Arnaudet G, Kauffmann B, Loquet A, Brûlé S, et al. The Pga59 cell wall protein is an amyloid forming protein involved in adhesion and biofilm establishment in the pathogenic yeast Candida albicans. NPJ Biofilms Microbiomes 2023; 9: 6.
23. Casas-Sanchez J, Alsina MA, Herrlein MK, Mestres C. Interaction between the antibacterial compound, oleuropein, and model membranes. Colloid Polym Sci 2007; 285: 1351-1360.
24. Li X, Liu Y, Jia Q, LaMacchia V, O’Donoghue K, Huang Z. A systems biology approach to investigate the antimicrobial activity of oleuropein. J Ind Microbiol Biotechnol 2016; 43: 1705-1717.
25. Bensehaila S, Ilias F, Saadi F, Zaouadi N. Phenolic compounds and antimicrobial activity of olive (Olea europaea L.) leaves. Asian J Dairy Food Res 2022; 41: 237-241.
26. Armbruster CR, Parsek MR. New insight into the early stages of biofilm formation. Proc Natl Acad Sci U S A 2018; 115: 4317-4319.
27. Guo W, Xu Y, Yang Y, Xiang J, Chen J, Luo D, et al. Antibiofilm effects of Oleuropein against Staphylococcus aureus: an in vitro study. Foods 2023; 12: 4301.
28. Nogueira JWA, Costa RA, da Cunha MT, Cavalcante TTA. Antibiofilm activity of natural substances derived from plants. Afr J Microbiol Res 2017; 11: 1051-1060.
29. Rahmanian N, Moulavi P, Ashrafi F, Sharifi A, Asadi S. Surface-functionalized UIO-66-NH2 for dual-drug delivery of vancomycin and amikacin against vancomycin-resistant Staphylococcus aureus. BMC Microbiol 2024; 24: 462.
30. Lashaki SB, Moulavi P, Ashrafi F, Sharifi A, Asadi S. Imipenem/Cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates. J Glob Antimicrob Resist 2025; 42: 15-27.
31. Isibor J, Eghubare A, Omoregie R. Germ tube formation in Candida albicans. Shiraz E Med J 2005; 6: 31817.
2. Hu Y, Niu Y, Ye X, Zhu C, Tong T, Zhou Y, et al. Staphylococcus aureus synergized with Candida albicans to increase the pathogenesis and drug resistance in cutaneous abscess and peritonitis murine models. Pathogens 2021; 10: 1036.
3. Carolus H, Van Dyck K, Van Dijck P. Candida albicans and Staphylococcus species: a threatening twosome. Front Microbiol 2019; 10: 2162.
4. Kojic EM, Darouiche RO. Candida infections of medical devices. Clin Microbiol Rev 2004; 17: 255-267.
5. Uppuluri P, Dinakaran H, Thomas DP, Chaturvedi AK, Lopez-Ribot JL. Characteristics of Candida albicans biofilms grown in a synthetic urine medium. J Clin Microbiol 2009; 47: 4078-4083.
6. Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 2002; 46: 1773-1780.
7. Ramage G, Coco B, Sherry L, Bagg J, Lappin DF. In vitro Candida albicans biofilm induced proteinase activity and SAP8 expression correlates with in vivo denture stomatitis severity. Mycopathologia 2012; 174: 11-19.
8. Baxter KJ, Sargison FA, Fitzgerald JR, McConnell G, Hoskisson PA. Time-lapse mesoscopy of Candida albicans and Staphylococcus aureus dual-species biofilms reveals a structural role for the hyphae of C. albicans in biofilm formation. Microbiology (Reading) 2024; 170: 001426.
9. Omar SH. Oleuropein in olive and its pharmacological effects. Sci Pharm 2010; 78: 133-154.
10. Shamshoum H, Vlavcheski F, Tsiani E. Anticancer effects of oleuropein. Biofactors 2017; 43: 517-528.
11. Ahamad J, Toufeeq I, Khan MA, Ameen MSM, Anwer ET, Uthirapathy S, et al. Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome. Phytother Res 2019; 33: 3112-3128.
12. Al-Rimawi F, Sbeih M, Amayreh M, Rahhal B, Mudalal S. Evaluation of the antibacterial and antifungal properties of oleuropein, olea Europea leaf extract, and thymus vulgaris oil. BMC Complement Med Ther 2024; 24: 297.
13. Bonincontro G, Scuderi SA, Marino A, Simonetti G. Synergistic Effect of plant compounds in combination with conventional antimicrobials against biofilm of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Pharmaceuticals (Basel) 2023; 16: 1531.
14. Vijakumaran U, Goh N-Y, Razali RA, Abdullah NAH, Yazid MD, Sulaiman N. Role of olive bioactive compounds in respiratory diseases. Antioxidants (Basel) 2023; 12: 1140.
15. Hassan J, Koohi MK, Sharifzadeh A, Babaei M, Moghadam S, Pourshaban Sharestani A. Extraction and purification of oleuropein from olive leaves. Nat Prod Res 2024; 1-9.
16. CLSI (2021). Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI supplement M100. Clinical and Laboratory Standards Institute.
17. Osman RB, Khoder G, Fayed B, Kedia RA, Elkareimi Y, Alharbi N. Influence of fabrication technique on adhesion and biofilm formation of Candida albicans to conventional, milled, and 3D-printed denture base resin materials: a comparative in vitro study. Polymers (Basel) 2023; 15: 1836.
18. Danchik C, Casadevall A. Role of cell surface hydrophobicity in the pathogenesis of medically-significant fungi. Front Cell Infect Microbiol 2021; 10: 594973.
19. Camaioni L, Ustyanowski B, Buisine M, Lambert D, Sendid B, Billamboz M, et al. Natural compounds with antifungal properties against Candida albicans and Identification of Hinokitiol as a promising antifungal drug. Antibiotics (Basel) 2023; 12: 1603.
20. Sobanska M, Scholz S, Nyman A-M, Cesnaitis R, Gutierrez Alonso S, Klüver N, et al. Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH). Environ Toxicol Chem 2018; 37: 657-670.
21. Xu S, Chen F, Zhang H, Huang Z-l, Li J, Wu D, et al. Development a high-throughput zebrafish embryo acute toxicity testing method based on OECD TG 236. Toxicol Mech Methods 2023; 33: 104-112.
22. Mourer T, El Ghalid M, Pehau-Arnaudet G, Kauffmann B, Loquet A, Brûlé S, et al. The Pga59 cell wall protein is an amyloid forming protein involved in adhesion and biofilm establishment in the pathogenic yeast Candida albicans. NPJ Biofilms Microbiomes 2023; 9: 6.
23. Casas-Sanchez J, Alsina MA, Herrlein MK, Mestres C. Interaction between the antibacterial compound, oleuropein, and model membranes. Colloid Polym Sci 2007; 285: 1351-1360.
24. Li X, Liu Y, Jia Q, LaMacchia V, O’Donoghue K, Huang Z. A systems biology approach to investigate the antimicrobial activity of oleuropein. J Ind Microbiol Biotechnol 2016; 43: 1705-1717.
25. Bensehaila S, Ilias F, Saadi F, Zaouadi N. Phenolic compounds and antimicrobial activity of olive (Olea europaea L.) leaves. Asian J Dairy Food Res 2022; 41: 237-241.
26. Armbruster CR, Parsek MR. New insight into the early stages of biofilm formation. Proc Natl Acad Sci U S A 2018; 115: 4317-4319.
27. Guo W, Xu Y, Yang Y, Xiang J, Chen J, Luo D, et al. Antibiofilm effects of Oleuropein against Staphylococcus aureus: an in vitro study. Foods 2023; 12: 4301.
28. Nogueira JWA, Costa RA, da Cunha MT, Cavalcante TTA. Antibiofilm activity of natural substances derived from plants. Afr J Microbiol Res 2017; 11: 1051-1060.
29. Rahmanian N, Moulavi P, Ashrafi F, Sharifi A, Asadi S. Surface-functionalized UIO-66-NH2 for dual-drug delivery of vancomycin and amikacin against vancomycin-resistant Staphylococcus aureus. BMC Microbiol 2024; 24: 462.
30. Lashaki SB, Moulavi P, Ashrafi F, Sharifi A, Asadi S. Imipenem/Cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates. J Glob Antimicrob Resist 2025; 42: 15-27.
31. Isibor J, Eghubare A, Omoregie R. Germ tube formation in Candida albicans. Shiraz E Med J 2005; 6: 31817.
| Files | ||
| Issue | Vol 17 No 2 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i2.18390 | |
| Keywords | ||
| Oleuropein; Candida albicans; Staphylococcus aureus; Adhesion; Biofilm | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Karzani S, Sharifzadeh A, Nayeri-Fasaei B, Khosravi AR, Hassan J, Sharifi A, Pourshaban Shahrestani A. Impact of oleuropein on Candida albicans and Staphylococcus aureus adhesion and its mediated toxicity in Zebrafish (Danio rerio) embryos. Iran J Microbiol. 2025;17(2):312-320.
