Effect of Allium cepa loaded polyacrylonitrile and polyvinyl pyrrolidone nanofibers on Candida albicans growth and the expression of CDR1 and CDR2 genes

Document Type : Original Articles


1 Department of Mycology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Mycology, Pasteur Institute of Iran, Tehran, Iran



Background and Purpose: This study aimed to assess the effect of Allium cepa ethanolic extract (ACE) loaded polyacrylonitrile (PAN) and polyvinyl pyrrolidone (PVP) nanofibers on Candida albicans (C. albicans) CDR1 and CDR2 genes expression.
Materials and Methods: The minimum inhibitory concentrations (MICs) of ACE against C. albicans ATCC 10231 and clinical fluconazole (FLC)-resistant C. albicans PFCC 93-902 were determined using the Clinical and Laboratory Standards Institute (CLSI) protocol (M27-Ed4) at a concentration range of 45.3-5800 µg/ml. The nanofibers containing ACE (60 wt%) were fabricated using the electrospinning technique. The expression of the CDR1 and CDR2 genes was studied in the fungus exposed to ACE loaded nanofibers and 0.5×MIC concentration of FLC using the real-time polymerase chain reaction.
Results: MIC50 and MIC90 of ACE against FLC-resistant C. albicans were 725 and 1450/mL, respectively. The expression of CDR1 (4.5-fold) and CDR2 (6.3-fold) were down-regulated after the exposure of FLC-resistant C. albicans to ACE-loaded nanofibers (P<0.05). Furthermore, the expression of CDR1 (2.8-fold) and CDR2 (3.2- fold) were up-regulated in FLC-treated C. albicans (P<0.05).
Conclusion: The results revealed that nanofibers containing ACE interact with drug resistant genes expressed in C. albicans. Further studies are recommended to investigate the mode of action and other biological activities of ACE-loaded nanofibers against C. albicans and other pathogenic fungi


 1. Santos RS, Loureiro KC, Rezende PS, Andrade LN, de Melo
Barbosa R, Santini A, et al. Innovative nanocompounds for
cutaneous administration of classical antifungal drugs: a
systematic review. J Dermato Treat. 2019; 30(6):617-26.
2. Seyedjavadi SS, Khani S, Eslamifar A, Ajdary S, Goudarzi M,
Halabian R, et al. The antifungal peptide MCh-AMP1 derived
Matricaria chamomilla inhibits Candida albicans growth
via inducing ROS generation and altering fungal cell membrane
permeability. Front Microbiol. 2020; 10:3150.
3. Bondaryk M, Kurzątkowski W, Staniszewska M. Antifungal
agents commonly used in the superficial and mucosal
candidiasis treatment: mode of action and resistance
Postepy Dermatol Alergol. 2013; 30(5):293.
4. Liu J-Y, Shi C, Wang Y, Li W-J, Zhao Y, Xiang M-J.
Mechanisms of azole resistance in
Candida albicans clinical
isolates from Shanghai, China. Res Microbiol. 2015;
5. Ikegbunam M, Ukamaka M, Emmanuel O. Evaluation of the
antifungal activity of aqueous and alcoholic extracts of six
spices. Ame J Plant Sci. 2016; 7(1):118-25.
6. Kyung KH. Antimicrobial properties of
Allium species. Curr
Opin Biotechnol. 2012; 23(2):142-7.
7. Teshika JD, Zakariyyah AM, Zaynab T, Zengin G, Rengasamy
KR, Pandian SK, et al. Traditional and modern uses of onion
bulb (
Allium cepa L.): a systematic review. Cri Rev Food Sci
Nutr. 2019; 59(sup1):S39-S70.
8. Goonoo N, Bhaw-Luximon A, Jhurry D. Drug loading and
release from electrospun biodegradable nanofibers. J Biomed
Nanotech. 2014; 10(9):2173-99.
9. Khan R, Shi X, Ahmad A, Mo X. Electrospinning of crude plant
extracts for antibacterial and wound healing applications: a
review. SM J Biomed Eng. 2018; 4(1):1-8.
10. Zhang W, Ronca S, Mele E. Electrospun nanofibres containing
antimicrobial plant extracts. Nanomaterials. 2017; 7(2):42.
11. Musavinasab-Mobarakeh SA, Shams-Ghahfarokhi M, RazzaghiAbyaneh M. Effect of Allium cepa on LAC1 gene expression
and physiological activities in
Cryptococcus neoformans. Curr
Med Mycol. 2021; 7(1):38.
12. Clinical and Laboratory Standards Institute (CLSI). Reference
method for broth dilution antifungal susceptibility testing of
yeasts; approved standard. 4th ed. CLSI standard M27-Ed4
Wayne, PA: CLSI. 2017.
13. Mostafa MS, Awad A. Association of ADH1 and DDR48
expression with azole resistance in Candida albicans. Int Arab J
Antimicrob Agents. 2015; 4(3):1-10.
14. Singh DD, Khare M, Singh V. Molecular Characterization of
Azole resistance mechanisms in
Candida albicans clinical
isolates from HIV-infected patients in India. Int J Pharm Sci
Res. 2014; 5(9):3924-31.
15. Shokrollahi M, Bahrami SH, Nazarpak MH, Solouk A.
Multilayer nanofibrous patch comprising chamomile loaded
carboxyethyl chitosan/poly (vinyl alcohol) and polycaprolactone
as a potential wound dressing. Int J Biol Macromol. 2020;
16. Lanzotti V. The analysis of onion and garlic. J Chromatogr A.
2006; 1112(1-2):3-22.
17. Singh B. Assessment of antifungal activity of onion (Allium
cepa l.) bulb extracts. Int J Educ Res. 2017; 3:35-6.
18. Kocić
Tanackov S, Dimić G, Mojović L, GvozdanovićVarga J,
Vuković A, Tomović V, Šojić B, Pejin J. Antifungal
activity of the onion (Allium cepa L.) essential oil against
Aspergillus, Fusarium and Penicillium species isolated from
food. J Food Process Preserv. 2017;41(4):e13050.
19. Irkin R, Korukluoglu M. Control of
Aspergillus niger with
garlic, onion and leek extracts. Afr J Biotechnol. 2007;
20. Bakht J, Khan S, Shafi M. In vitro antimicrobial activity of
Allium cepa (dry bulbs) against Gram positive and Gramnegative bacteria and fungi. Pak J Pharm Sci. 2014;
21. Hamza HJ. Antimicrobial activity of some plant extracts on
microbial pathogens isolated from Hilla city hospitals, Iraq. Med
J Babylon. 2015; 12(2):398-407.
22. Shams-Ghahfarokhi M, Shokoohamiri M-R, Amirrajab N,
Moghadasi B, Ghajari A, Zeini F, et al. In vitro antifungal
activities of
Allium cepa, Allium sativum and ketoconazole
against some pathogenic yeasts and dermatophytes. Fitoterapia.
2006; 77(4):321-3.
23. Gomaa EZ. Antimicrobial, antioxidant and antitumor activities
of silver nanoparticles synthesized by
Allium cepa extract: a
green approach. J Genet Eng and Biotechnol. 2017; 15(1):49-57.
24. Jeckson TA, Neo YP, Sisinthy SP, Gorain B. Delivery of
therapeutics from layer-by-layer electrospun nanofiber matrix
for wound healing: An update. J Pharm Sci. 2020; 110(2):635-53
25. Esenturk I, Gumrukcu S, Özdabak Sert AB, Kök FN, Döşler S,
Gungor S, et al. Silk-fibroin-containing nanofibers for topical
sertaconazole delivery: preparation, characterization, and
antifungal activity. Int J Polym Mater. 2020; 70(9):1-18.
26. Motealleh B, Zahedi P, Rezaeian I, Moghimi M, Abdolghaffari
AH, Zarandi MA. Morphology, drug release, antibacterial, cell
proliferation, and histology studies of chamomile
loaded wound
dressing mats based on electrospun nanofibrous poly
caprolactone)/polystyrene blends. J Biomed Mater Res B.
2014; 102(5):977-87.
27. Semnani K, Shams-Ghahfarokhi M, Afrashi M, Fakhrali A,
Semnani D. Antifungal activity of eugenol loaded electrospun
pan nanofiber mats against
Candida albicans. Curr Drug Deliv.
2018; 15(6):860-6.
28. Parsameher N, Rezaei S, Khodavasiy S, Salari S, Hadizade S,
Kord M, et al. Effect of biogenic selenium nanoparticles on
ERG11 and CDR1 gene expression in both fluconazole-resistant
Candida albicans isolates. Curr Med Mycol.
2017; 3(3):16-20.
29. Xu Y, Sheng F, Zhao J, Chen L, Li C. ERG11 mutations and
expression of resistance genes in fluconazole-resistant
isolates. Arch Microbiol. 2015; 197(9):1087-93.
30. Pourakbari B, Teymuri M, Mahmoudi S, K Valian S, Movahedi
Z, Eshaghi H, et al. Expression of major efflux pumps in
Candida albicans. Infect Disord Drug
Target. 2017; 17(3):178-84.
31. Chen L, Xu Y, Zhou C, Zhao J, Li C, Wang R. Overexpression
of CDR1 and CDR2 genes plays an important role in
fluconazole resistance in
Candida albicans with G487T and
T916C mutations. J Int Med Res. 2010; 38(2):536-45.
32. Morschhäuser J. The genetic basis of fluconazole resistance
development in
Candida albicans. Biochim Biophys Acta.
33. Shao J, Zhang M, Wang T, Li Y, Wang C. The roles of CDR1,
CDR2, and MDR1 in kaempferol-induced suppression with
Candida albicans. Pharm Biol. 2016;
34. Herman A, Herman AP. Herbal products and their active
constituents used alone and in combination with antifungal drugs
against drug-resistant
Candida sp. Antibiotics (Basel).