Anti-fungal efficacy of Carvacrol against Candida glabrata clinical isolates of vulvovaginal candidiasis
DOI:
https://doi.org/10.14719/pst.3140Keywords:
Antimicrobial resistance, Candida glabrata, Carvacrol, Clinical isolates, Fluconazole, Vulvovaginal candidiasis, WHO FPPLAbstract
Fungal infections affect over 1 billion people worldwide each year, including superficial infections like athlete's foot and more severe systemic infections. Fungal diseases are responsible for an estimated 1.5 million deaths annually, a figure comparable to or exceeding the mortality rate of diseases like malaria or tuberculosis. The limited arsenal of available antifungal drugs, coupled with the emergence of drug-resistant fungal strains, has increased this concern. Therefore, there is a significant need to explore alternative therapeutics to overcome fungal pathogens. Carvacrol, phenolic monoterpenoids, is present in essential oils of many plants and is known for its biological and pharmacological properties. In the present study, the efficacy of carvacrol was investigated against four Candida glabrata strains isolated from patients of vulvovaginal candidiasis, which have shown varying extents of susceptibility against fluconazole. Carvacrol, a phytoactive monoterpene phenol, has shown a minimum inhibitory concentration (MIC50) ranging from 75 to 125 µg/mL and minimum fungicidal concentration of 150 and 175 µg/mL for all clinical isolates, including wild-type strains. Carvacrol, in combination with fluconazole, has shown a strong synergism against wild type C. glabrata with a FIC index value of 0.156. Preliminary mechanistic investigations unveiled that exposure to carvacrol significantly reduced cell surface hydrophobicity and ergosterol content in all strains. In conclusion, carvacrol holds promising potential as an effective antifungal agent against C. glabrata, which is categorized as high priority in the first fungal pathogen priority list of the World Health Organisation released in 2022 for highlighting priority areas for action, including the development of effective therapeutic solution.
Downloads
References
Bongomin F, Gago S, Oladele RO, Denning DW. Global and multi-national prevalence of fungal diseases—estimate precision. Journal of Fungi. 2017;3(4). http://doi.org/10.3390/jof3040057
Vallabhaneni S, Mody RK, Walker T, Chiller T. The global burden of fungal diseases. Infectious Disease Clinics. 2016 Mar 1;30(1):1-1. http://dx.doi.org/10.1016/j.idc.2015.10.004
Kontoyiannis DP. Antifungal resistance: An emerging reality and a global challenge. Journal of Infectious Diseases. 2017;216(Suppl 3):S431-35. http://doi.org/10.1093/infdis/jix179
Gaspar-Cordeiro A, Amaral C, Pobre V, Antunes W, Petronilho A, Paixão P et al. Copper acts synergistically with fluconazole in Candida glabrata by compromising drug efflux, sterol metabolism and zinc homeostasis. Front Microbiol. 2022;13:920574. https://doi.org/10.3389/fmicb.2022.920574
Fisher MC, Denning DW. The WHO fungal priority pathogens list as a game-changer. Nat Rev Microbiol. 2023;21(4):211-12. https://doi.org/10.1038/s41579-023-00861-x
Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: A systematic review. Lancet Infect Dis. 2018;18(11): e339-47. Available from: http://dx.doi.org/10.1016/S1473-3099(18)30103-8
Ksiezopolska E, Schikora-Tamarit MÀ, Beyer R, Nunez-Rodriguez JC, Schüller C, Gabaldón T. Narrow mutational signatures drive acquisition of multidrug resistance in the fungal pathogen Candida glabrata. Current Biology. 2021;31(23):5314-26.e10. http://doi.org/ 10.1016/j.cub.2021.09.084
Deorukhkar SC. Virulence traits contributing to pathogenicity of Candida species. J Microbiol Exp. 2017;5(1):8-11. http://doi.org/10.15406/jmen.2017.05.00140
Gupta P, Gupta S, Sharma M, Kumar N, Pruthi V, Poluri KM. Effectiveness of phytoactive molecules on transcriptional expression, biofilm matrix and cell wall components of Candida glabrata and its clinical isolates. ACS Omega. 2018;3(9):12201-14. https://doi.org/10.1021/acsomega.8b01856
Wang Q, Cai X, Li Y, Zhao J, Liu Z, Jiang Y et al. Molecular identification, antifungal susceptibility and resistance mechanisms of pathogenic yeasts from the China antifungal resistance surveillance trial (CARST-fungi) study. Front Microbiol. 2022 Oct 6;13. https://doi.org/10.3389/fmicb.2022.1006375
Aljaafari MN, Alali AO, Baqais L, Alqubaisy M, Alali M, Molouki A et al. An overview of the potential therapeutic applications of essential oils. Molecules. 2021;26(3). https://doi.org/ 10.3390/molecules26030628
Can Baser K. Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Curr Pharm Des. 2008;14(29):3106-19. http://doi.org/10.2174/138161208786404227
Gandova V, Lazarov A, Fidan H, Dimov M, Stankov S, Denev P et al. Physicochemical and biological properties of carvacrol. Open Chem. 2023;21(1). https://doi.org/10.1515/chem-2022-0319
Memar MY, Raei P, Alizadeh N, Aghdam MA, Kafil HS. Carvacrol and thymol: Strong antimicrobial agents against resistant isolates. Reviews in Medical Microbiology. 2017;28(2):63-68. https://doi.org /10.1097/MRM.0000000000000100
Miranda-Cadena K, Marcos-Arias C, Mateo E, Aguirre-Urizar JM, Quindós G, Eraso E. In vitro activities of carvacrol, cinnamaldehyde and thymol against Candida biofilms. Biomedicine and Pharmacotherapy. 2021 Nov 1;143. https://doi.org/10.1016/j.biopha.2021.112218
Gupta P, Chanda R, Rai N, Kataria VK, Kumar N. Antihypertensive, Amlodipine besilate inhibits growth and biofilm of human fungal pathogen Candida. Assay Drug Dev Technol. 2016;14(5):291-97. https://doi.org/10.1089/adt.2016.714
Fahimirad S, Abtahi H, Razavi SH, Alizadeh H, Ghorbanpour M. Production of recombinant antimicrobial polymeric protein beta casein-E 50-52 and its antimicrobial synergistic effects assessment with thymol. Molecules. 2017 Jun 1;22(6). https://doi.org/10.3390/molecules22060822
Priya A, Selvaraj A, Divya D, Karthik Raja R, Pandian SK. In vitro and in vivo anti-infective potential of thymol against early childhood caries causing dual species Candida albicans and Streptococcus mutans. Front Pharmacol. 2021 November;12:1-16. https://doi.org/10.3389/fphar.2021.760768
RR Goswami, SD Pohare, JS Raut, S Mohan Karuppayil. Cell surface hydrophobicity as a virulence factor in Candida albicans. Biosci Biotechnol Res Asia. 2017;14(4):1503-11. http://dx.doi.org/10.13005/bbra/2598
Nagoor Meeran MF, Javed H, Taee H Al, Azimullah S, Ojha SK. Pharmacological properties and molecular mechanisms of thymol: Prospects for its therapeutic potential and pharmaceutical development. Frontiers in Pharmacology. Frontiers Media SA. 2017;Vol. 8. https://doi.org/10.3389/fphar.2017.00380
Shariati A, Didehdar M, Razavi S, Heidary M, Soroush F, Chegini Z. Natural compounds: A hopeful promise as an antibiofilm agent against Candida species. Frontiers in Pharmacology. Frontiers Media SA. 2022;Vol. 13. https://doi.org/10.3389/fphar.2022.917787
Vu BG, Scott Moye-Rowley W. Azole-resistant alleles of ERG11 in Candida glabrata trigger activation of the Pdr1 and Upc2A transcription factors. Antimicrob Agents Chemother. 2022;15;66(3):e0209821. https://doi.org/10.1128/AAC.02098-21
Lotfali E, Erami M, Fattahi M, Nemati H, Ghasemi Z, Mahdavi E. Analysis of molecular resistance to azole and echinocandin in Candida species in patients with vulvovaginal candidiasis. Curr Med Mycol. 2022 Jun 1;8(2):1-7. https://doi.org/10.18502/cmm.8.2.10326
Sasani E, Yadegari MH, Khodavaisy S, Rezaie S, Salehi M, Getso MI. Virulence factors and azole-resistant mechanism of Candida tropicalis isolated from Candidemia. Mycopathologia. 2021;186(6):847-56. https://doi.org/10.1007/s11046-021-00580-y.
Carradori S, Ammazzalorso A, De Filippis B, ?ahin AF, Akdemir A, Orekhova A et al. Azole-based compounds that are active against Candida biofilm: In vitro, in vivo and in silico studies. Antibiotics. 2022 Oct 1;11(10). https://doi.org/10.3390/antibiotics11101375
El Said M, Badawi H, Gamal D, Salem D, Dahroug H, El-Far A. Detection of ERG11 gene in fluconazole resistant urinary Candida isolates. Egypt J Immunol. 2022 Oct 1;29(4):134-47. https://doi.org/10.55133/eji.290413
Marchese A, Orhan IE, Daglia M, Barbieri R, Di Lorenzo A, Nabavi SF et al. Antibacterial and antifungal activities of thymol: A brief review of the literature. Food Chem. 2016;210:402-14. http://dx.doi.org/10.1016/j.foodchem.2016.04.111
Sharifzadeh A, Khosravi AR, Shokri H, Shirzadi H. Potential effect of 2-isopropyl-5-methylphenol (thymol) alone and in combination with fluconazole against clinical isolates of Candida albicans, C. glabrata and C. krusei. J Mycol Med. 2018 Jun 1;28(2):294-99. http://dx.doi.org/10.1016/j.mycmed.2018.04.002
Chaillot J, Tebbji F, Remmal A, Boone C, Brown GW, Bellaoui M et al. The monoterpene carvacrol generates endoplasmic reticulum stress in the pathogenic fungus Candida albicans. Antimicrob Agents Chemother. 2015;59(8):4584-92. https://doi.org/ 0.1128/AAC.00551-15
Ahmad A, Khan A, Akhtar F, Yousuf S, Xess I, Khan LA et al. Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida. European Journal of Clinical Microbiology and Infectious Diseases. 2011 Jan;30(1):41-50. https://doi.org/ 10.1007/s10096-010-1050-8
Niu C, Wang C, Yang Y, Chen R, Zhang J, Chen H et al. Carvacrol induces Candida albicans apoptosis associated with Ca2+/calcineurin pathway. Front Cell Infect Microbiol. 2020 April;10:1-12. https://doi.org/ 10.3389/fcimb.2020.00192
Lima IO, De Oliveira Pereira F, De Oliveira WA, De Oliveira Lima E, Menezes EA, Cunha FA et al. Antifungal activity and mode of action of carvacrol against Candida albicans strains. Journal of Essential Oil Research. 2013;25(2):138-42. https://doi.org/10.1080/10412905.2012.754728
Rao A, Zhang Y, Muend S, Rao R. Mechanism of antifungal activity of terpenoid phenols resembles calcium stress and inhibition of the TOR pathway. Antimicrob Agents Chemother. 2010;54(12):5062-69. https://doi.org/10.1128/AAC.01050-10
Kaskatepe B, Erdem SA, Ozturk S, Oz ZS, Subasi E, Koyuncu M et al. Antifungal and anti-virulent activity of Origanum majorana L. essential oil on Candida albicans and in vivo toxicity in the Galleria mellonella larval model. Molecules. 2022;27(3). https://doi.org/10.3390/molecules27030663
Rajkowska K, Kunicka-Styczy?ska A, Peczek M. Hydrophobic properties of Candida spp. under the influence of selected essential oils. Acta Biochim Pol. 2015;62(4):663-68. https://doi.org/10.18388/abp.2015_1096
Downloads
Published
Versions
- 22-07-2024 (2)
- 21-07-2024 (1)
How to Cite
Issue
Section
License
Copyright (c) 2024 Darshan Kumar, Ayesha Ansari, Nishant Rai, Amit Gupta, Navin Kumar
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright and Licence details of published articles
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Open Access Policy
Plant Science Today is an open access journal. There is no registration required to read any article. All published articles are distributed under the terms of the Creative Commons Attribution License (CC Attribution 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited (https://creativecommons.org/licenses/by/4.0/). Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
