Sensitization of Candida albicans biofilms to fluconazole by terpenoids of plant origin

Doke, Sonali Kashinath; Raut, Jayant S.; Dhawale, Shashikant C.; Karuppayil, Sankunny Mohan

doi:10.2323/jgam.60.163

Cited by 60 publications

(40 citation statements)

References 22 publications

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“…The most significant IC 50 values were ranging 0.063-1.23 μM against C. krusei, C. glabrata, and C. albicans [38]. Fractional inhibitory concentration indices (FICI) for carvacrol-fluconazole and eugenolfluconazole combinations for C. albicans biofilm formation were 0.311 and 0.25, respectively [39]. Eugenol treatment significantly reduced the adherence and metabolic activity of biofilms of C. albicans isolated from the oral cavity of HIV infected patients [40].…”

Section: Antifungal Activity Of Eugenolmentioning

confidence: 99%

Versatile and Synergistic Potential of Eugenol: A Review

Raja¹

2015

Pharm Anal Acta

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Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is the phenolic component of essential oil and the main constituent of Eugenia caryophyllata, Ocimmum gratissimum and several others medicinal plant. In view of its nonmutagenic and non-carcinogenic properties, eugenol is generally regarded as safe by the Food and Agricultural Organization of the United Nations. Eugenol has been recently shown to be effective for antimicrobials and treatment of different life threatening diseases including sepsis, leishmaniasis, and cancer. However overall, activity of eugenol is not discussed elsewhere. In this review, we discuss the current understanding of the mechanisms involved the antioxidant, antimicrobial, anticancer and anti-inflammatory potential of eugenol.

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Section: Antifungal Activity Of Eugenolmentioning

confidence: 99%

Versatile and Synergistic Potential of Eugenol: A Review

Raja¹

2015

Pharm Anal Acta

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“…Previous investigations demonstrated that carvacrol is one of the potent monoterpenes against C. albicans, impeding the growth of different morphological forms, including yeast, hyphae, and the highly drug-resistant biofilm (9)(10)(11). Recent studies have shown that the monoterpenes carvacrol and eugenol, but not thymol, synergize with the azole antifungal fluconazole and inhibit planktonic growth and biofilm in clinical resistant strains (12). Interestingly, carvacrol has been proved to be an effective treatment against vaginal candidiasis in an immunosuppressed rat model (13).…”

mentioning

confidence: 99%

The Monoterpene Carvacrol Generates Endoplasmic Reticulum Stress in the Pathogenic Fungus Candida albicans

Chaillot

Tebbji

Remmal

et al. 2015

Antimicrob Agents Chemother

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The monoterpene carvacrol, the major component of oregano and thyme oils, is known to exert potent antifungal activity against the pathogenic yeast Candida albicans. This monoterpene has been the subject of a considerable number of investigations that uncovered extensive pharmacological properties, including antifungal and antibacterial effects. However, its mechanism of action remains elusive. Here, we used integrative chemogenomic approaches, including genome-scale chemical-genetic and transcriptional profiling, to uncover the mechanism of action of carvacrol associated with its antifungal property. Our results clearly demonstrated that fungal cells require the unfolded protein response (UPR) signaling pathway to resist carvacrol. The mutants most sensitive to carvacrol in our genome-wide competitive fitness assay in the yeast Saccharomyces cerevisiae expressed mutations of the transcription factor Hac1 and the endonuclease Ire1, which is required for Hac1 activation by removing a nonconventional intron from the 3= region of HAC1 mRNA. Confocal fluorescence live-cell imaging revealed that carvacrol affects the morphology and the integrity of the endoplasmic reticulum (ER). Transcriptional profiling of pathogenic yeast C. albicans cells treated with carvacrol demonstrated a bona fide UPR transcriptional signature. Ire1 activity detected by the splicing of HAC1 mRNA in C. albicans was activated by carvacrol. Furthermore, carvacrol was found to potentiate antifungal activity of the echinocandin antifungal caspofungin and UPR inducers dithiothreitol and tunicamycin against C. albicans. This comprehensive chemogenomic investigation demonstrated that carvacrol exerts its antifungal activity by altering ER integrity, leading to ER stress and the activation of the UPR to restore protein-folding homeostasis.F ungal pathogens represent a serious risk to the growing population of immunocompromised individuals resulting from the increasing success of organ and bone marrow transplantation, immune-suppressive cancer chemotherapy, premature births, and the AIDS pandemic. Candida albicans is a diploid ascomycete yeast that is an important commensal and opportunistic pathogen in humans. Systemic infections resulting from C. albicans are on the rise and are associated with mortality rates of 50% or greater despite currently available antifungal therapy (1-3). Current therapeutic options are limited to treatment with three longstanding antifungal classes, the polyenes, azoles, and echinocandins (4). These compounds target the specific fungal biological process of ergosterol metabolism (azoles and polyenes) and cell wall ␤-1,3-glucan synthesis (echinocandins). However, these drugs have serious side effects such as nephrotoxicity and/or create complications such as resistance due to their fungistatic rather than fungicidal characteristics (4-6). There is, thus, an urgent need for new strategies to identify novel protein targets and bioactive molecules for antifungal therapeutic intervention.Plants are an interesting reservoir of s...

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“…In vitro studies have shown satisfactory results regarding the association between natural products and conventional antimicrobials directed for antifungal therapy [13][14][15]. In a study conducted in India [15], the authors showed that the addition of eugenol and carvacrol to fluconazole have significantly reduced the concentration of the latter, in inhibition of biofilm growth by C. albicans.…”

Section: Discussionmentioning

confidence: 99%

“…In a study conducted in India [15], the authors showed that the addition of eugenol and carvacrol to fluconazole have significantly reduced the concentration of the latter, in inhibition of biofilm growth by C. albicans. According to the aforementioned study, these terpenes cause instability in the fungal membrane and intervention in specific signals, facilitating greater fluconazole influx to the intracellular environment and culminating in inhibition of biofilm formation [15].…”

Section: Discussionmentioning

confidence: 99%

“…Based on that, recent studies had given evidence to antimicrobial compounds extracted from plants, in a form of essential oils, crude extracts, and molecules, such as flavonoids and terpenes [8,11,12]. Recent studies have also focused on the association between natural products and conventional pharmacological agents in order to achieve better efficacy of treatments [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Antifungal Activity of Eugenol and its Association with Nystatin on Candida albicans

Silva

Santos

Cavalcanti

et al. 2017

Pesqui. bras. odontopediatria clín. integr.

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Objective: To evaluate the anti-Candida effect of eugenol and its antimicrobial interaction with nystatin. Material and Methods: The antimicrobial potential was assessed by microdilution technique (M27A3 reference method), by determining the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) against C. albicans (ATCC 90028). The possible action of eugenol on the fungal cell wall was evaluated with the assistance of the osmotic protector sorbitol (0.8 M). The antimicrobial interaction with nystatin was assessed through the checkerboard method. All tests were performed in triplicate. Results: All groups showed reductions in PI and GBI values and improvements in oral health knowledge, but IG1 and IG2 showed statistically significant differences in these variables compared to CG. Conclusion: The eugenol has antifungal activity against C. albicans and its mechanism of action is probably not related to damage to the fungal cell wall. Association between eugenol and nystatin was not found to be an advantageous possibility for growth inhibition of C. albican.

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Sensitization of Candida albicans biofilms to fluconazole by terpenoids of plant origin

Abstract: Infections associated with the biofilms of

Cited by 60 publications

References 22 publications

Versatile and Synergistic Potential of Eugenol: A Review

Versatile and Synergistic Potential of Eugenol: A Review

The Monoterpene Carvacrol Generates Endoplasmic Reticulum Stress in the Pathogenic Fungus Candida albicans

Antifungal Activity of Eugenol and its Association with Nystatin on Candida albicans

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