Antibacterial effect of Curcumin encapsulated in polymersome nanoparticles on the expression of efflux pump MDR1 gene in fluconazole resistant isolates of Candida albicans
Subject Areas : Biotechnological Journal of Environmental Microbiology
ُSahar Pourasgar
1
(Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran. )
Aida Bejari
2
(Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran)
Mahkameh Hedayatsafa
3
(Department of Natural Resources, Faculty of Sciences, university of parma, Italy.)
Mahdi Shahriarinour
4
(Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran. )
Najmeh Ranji
5
(Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran. )
Keywords: Candida albicans, Curcumin, Nanoparticles, MDR1, qRT-PCR,
Abstract :
Curcumin, a natural product of turmeric, is known for its antibacterial and antifungal properties. Candida albicans is a major fungal pathogen with high mortality rate, particularly in immunocompromised patients. This study aimed to evaluate the effect of curcumin encapsulated in nanoparticles (polymersomes) in combination with fluconazole on the expression of the MDRI gene in drug-resistant isolates of C. albicans. This descriptive cross-sectional study involved obtaining 50 clinical samples, from women with vulvovaginal infections at Al-Zahra hospital (Rasht, Iran). After identifying the strains, resistance to fluconazole was assessed using disc diffusion and broth dilution methods. Six fluconazole-resistant isolates of C. albicans were treated with ½ MIC fluconazole (control) alone and in combination with curcumin encapsulated in nanoparticles. After 24 hours, the two cell groups were cultured on Sabouraud dextrose agar (SDA) to estimate the cell death rate. The expression of the MDR1 gene was quantitatively investigated using the qRT-PCR method in treated and untreated isolates. Our finding indicated that combined therapy with ½ MIC fluconazole and curcumin encapsulated in nanoparticles (at a concentration of 400µg/ml) reduced fungal growth by up to 50% within during 24 hours. In treated cells, qRT-PCR analysis revealed a decrease in MDR1 gene expression compared to untreated cells. Curcumin appears to enhance the effectiveness of fluconazole in fluconazole-resistant isolates by reducing MDR1 gene expression.
Alalwan, H., Rajendran, R., Lappin, D. F., Combet, E., Shahzad, M., Robertson, D., . . . Ramage, G. (2017). The anti-adhesive effect of curcumin on Candida albicans biofilms on denture materials. Frontiers in Microbiology, 8, 258345.
Awanish Kumar, A. K., Sanjiveeni Dhamgaye, S. D., Maurya, I., Ashutosh Singh, A. S., Monika Sharma, M. S., & Rajendra Prasad, R. P. (2014). Curcumin targets cell wall integrity via calcineurin-mediated signaling in Candida albicans.
Baldesi, O., Bailly, S., Ruckly, S., Lepape, A., L'Heriteau, F., Aupee, M., . . . Berger-Carbonne, A. (2017). ICU-acquired candidaemia in France: epidemiology and temporal trends, 2004–2013–a study from the REA-RAISIN network. Journal of Infection, 75(1), 59-67.
Balouiri, M., Sadiki, M., & Ibnsouda, S. K. (2016). Methods for in vitro evaluating antimicrobial activity: A review. Journal of pharmaceutical analysis, 6(2), 71-79.
Bergin, S. A., Doorley, L. A., Rybak, J., Wolfe, K. H., Butler, G., Cuomo, C. A., & Rogers, P. D. (2023). Analysis of clinical Candida parapsilosis isolates reveals copy number variation in key fluconazole resistance genes. bioRxiv, 2023.2012. 2013.571446.
Bezerra, B. M. S., y Araújo, S. E. D. d. M., Alves-Júnior, J. d. O., Damasceno, B. P. G. d. L., & Oshiro-Junior, J. A. (2024). The Efficacy of Hybrid Vaginal Ovules for Co-Delivery of Curcumin and Miconazole against Candida albicans. Pharmaceutics, 16(3), 312.
Charles, M. P., Kali, A., & Joseph, N. M. (2015). Performance of chromogenic media for Candida in rapid presumptive identification of Candida species from clinical materials. Pharmacognosy Research, 7(Suppl 1), S69.
Chen, L., Xu, Y., Zhou, C., Zhao, J., Li, C., & Wang, R. (2010). Overexpression of CDR1 and CDR2 genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C mutations. Journal of International Medical Research, 38(2), 536-545.
Cheraghipour, K., Ezatpour, B., Masoori, L., Marzban, A., Sepahvand, A., Rouzbahani, A. K., . . . Mahmoudvand, H. (2021). Anti-Candida activity of curcumin: A systematic review. Current drug discovery technologies, 18(3), 379-390.
Garcia-Gomes, A., Curvelo, J., Soares, R. A., & Ferreira-Pereira, A. (2012). Curcumin acts synergistically with fluconazole to sensitize a clinical isolate of Candida albicans showing a MDR phenotype. Medical mycology, 50(1), 26-32.
Hajifathali, S., Lesan, S., Lotfali, E., Salimi-Sabour, E., & Khatibi, M. (2023). Investigation of the antifungal effects of curcumin against nystatin-resistant Candida albicans. Dental Research Journal, 20(1), 50.
Hu, Y., Zhang, J., Kong, W., Zhao, G., & Yang, M. (2017). Mechanisms of antifungal and anti-aflatoxigenic properties of essential oil derived from turmeric (Curcuma longa L.) on Aspergillus flavus. Food Chemistry, 220, 1-8.
Ishikane, M., Hayakawa, K., Kutsuna, S., Takeshita, N., & Ohmagari, N. (2016). Epidemiology of blood stream infection due to Candida species in a tertiary care hospital in Japan over 12 years: importance of peripheral line-associated candidemia. PLoS One, 11(10), e0165346.
Jeanmonod, R., Jeanmonod, D., Christopherson, N., & Spivey, R. (2019). Vaginal candidiasis (vulvovaginal candidiasis). StatPearls.
Kali, A., Bhuvaneshwar, D., Charles, P. M., & Seetha, K. S. (2016). Antibacterial synergy of curcumin with antibiotics against biofilm producing clinical bacterial isolates. Journal of basic and clinical pharmacy, 7(3), 93.
Khalil, O. A. K., de Faria Oliveira, O. M. M., Vellosa, J. C. R., de Quadros, A. U., Dalposso, L. M., Karam, T. K., . . . Khalil, N. M. (2012). Curcumin antifungal and antioxidant activities are increased in the presence of ascorbic acid. Food Chemistry, 133(3), 1001-1005.
Lee, Y. S., Chen, X., Widiyanto, T. W., Orihara, K., Shibata, H., & Kajiwara, S. (2022). Curcumin affects function of Hsp90 and drug efflux pump of Candida albicans. Frontiers in Cellular and Infection Microbiology, 12, 944611.
Monk, B. C., & Keniya, M. V. (2021). Roles for structural biology in the discovery of drugs and agrochemicals targeting sterol 14α-demethylases. Journal of Fungi, 7(02), 67.
Motahhary Tashi, H., & Ranji, N. (2017). Study on oprD mutation and imipenem resistance in Pseudomonas aeruginosa isolates in Gilan province. Journal of Microbial World, 10(1), 26-36.
Narayanan, V. S., Muddaiah, S., Shashidara, R., Sudheendra, U., Deepthi, N., & Samaranayake, L. (2020). Variable antifungal activity of curcumin against planktonic and biofilm phase of different candida species. Indian Journal of Dental Research, 31(1), 145-148.
Pakizehkar, S., Ranji, N., Sohi, A. N., & Sadeghizadeh, M. (2020). Polymersome‐assisted delivery of curcumin: a suitable approach to decrease cancer stemness markers and regulate miRNAs expression in HT29 colorectal cancer cells. Polymers for Advanced Technologies, 31(1), 160-177.
Paul, S., Singh, S., Sharma, D., Chakrabarti, A., Rudramurthy, S. M., & Ghosh, A. K. (2020). Dynamics of in vitro development of azole resistance in Candida tropicalis. Journal of Global Antimicrobial Resistance, 22, 553-561.
Rad, K. K., Falahati, M., Roudbary, M., Farahyar, S., & Nami, S. (2016). Overexpression of MDR-1 and CDR-2 genes in fluconazole resistance of Candida albicans isolated from patients with vulvovaginal candidiasis. Current medical mycology, 2(4), 24.
Rahbar Takrami, S., Ranji, N., & Sadeghizadeh, M. (2019). Antibacterial effects of curcumin encapsulated in nanoparticles on clinical isolates of Pseudomonas aeruginosa through downregulation of efflux pumps. Molecular biology reports, 46, 2395-2404.
Rajasekar, V., Darne, P., Prabhune, A., Kao, R. Y., Solomon, A. P., Ramage, G., . . . Neelakantan, P. (2021). A curcumin-sophorolipid nanocomplex inhibits Candida albicans filamentation and biofilm development. Colloids and Surfaces B: Biointerfaces, 200, 111617.
Ranji, N. (2014). Investigation of Survivin and hTERT gene expression in gastric adenocarcinoma cell line (AGS) treated by nano Curcumin. Cellular and Molecular Research (Iranian Journal of Biology), 27(2), 233-241.
Ranji, N., & Rahbar Takrami, S. (2017). Role of mexZ gene in ciprofloxacin resistance in Pseudomonas aeruginosa isolates in Guilan province. Studies in Medical Sciences, 27(10), 902-913. Sadiq, A., Ahmad, S., Ali, R., Ahmad, F., Ahmad, S., Zeb, A., . . . Siddique, A. N. (2016). Antibacterial and antifungal potentials of the solvents extracts from Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum. BMC complementary and alternative medicine, 16, 1-8. Sharma, P., Blackburn, R. C., Parke, C. L., McCullough, K., Marks, A., & Black, C. (2011). Angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non‐diabetic chronic kidney disease. Cochrane Database of Systematic Reviews(10). Soliman, S. S., Semreen, M. H., El-Keblawy, A. A., Abdullah, A., Uppuluri, P., & Ibrahim, A. S. (2017). Assessment of herbal drugs for promising anti-Candida activity. BMC complementary and alternative medicine, 17, 1-9. Tsopmene, U. J., Tokam Kuaté, C. R., Kayoka-Kabongo, P. N., Bisso, B. N., Metopa, A., Mofor, C. T., & Dzoyem, J. P. (2024). Antibiofilm Activity of Curcumin and Piperine and Their Synergistic Effects with Antifungals against Candida albicans Clinical Isolates. Scientifica, 2024. Vinodkumar, S., Nakkeeran, S., & Renukadevi, P. (2017). Biocontrol potentials of antimicrobial peptide producing Bacillus species: multifaceted antagonists for the management of stem rot of carnation caused by Sclerotinia sclerotiorum. Frontiers in Microbiology, 8, 254948. Zhang, H., Xu, Q., Li, S., Ying, Y., Zhang, Z., Zeng, L., . . . Huang, S. (2019). Gene Expression Analysis of Key Players Associated with Fluconazole Resistance in Candida albicans. Jundishapur Journal of Microbiology, 12(7). Zhou, Z., Wang, S., Fan, P., Meng, X., Cai, X., Wang, W., . . . Su, J. (2024). Borneol serves as an adjuvant agent to promote the cellular uptake of curcumin for enhancing its photodynamic fungicidal efficacy against Candida albicans. Journal of Photochemistry and Photobiology B: Biology, 112875.