Antifungal activity of tyrosol and farnesol used in combination against <i>Candida</i>
 species in the planktonic state or forming biofilms

Monteiro, Douglas Roberto; Arias, Laís Salomão; Fernandes, Rosa Áurea Quintella; Silva, L.F. Deszo da; Castilho, M.O.V.F. de; Rosa, TO; Vieira, Ana Paula Miranda; Straioto, Fabiana Gouveia; Barbosa, Débora Barros; Delbem, Alexandre Cláudio Botazzo

doi:10.1111/jam.13513

Cited by 41 publications

(28 citation statements)

References 29 publications

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“…Concerning our growth-based experiments, a significant inhibitory effect was induced by the tyrosol concentration used, which is in line with previous investigations concerned with C. albicans, C. tropicalis, and C. krusei (5,7,14). The observed significant downregulation of ribosome biogenesis genes is concordant with this marked growth inhibition.…”

Section: Discussionsupporting

confidence: 91%

“…Based on the gene expression profile of C. albicans, tyrosol affects cell cycle regulation, DNA replication, and chromosome segregation (3). Besides its role in fungal physiology, tyrosol also possesses remarkable antifungal activity at supraphysiological concentrations (1 to 50 mM) against both planktonic and sessile Candida populations; therefore, its potential role in certain aspects of antifungal therapy has been postulated, e.g., in catheter lock therapy (5)(6)(7).…”

mentioning

confidence: 99%

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Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Jakab

Tóth

Nagy

et al. 2019

Appl Environ Microbiol

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Tyrosol plays a key role in fungal morphogenesis and biofilm development. Also, it has a remarkable antifungal effect at supraphysiological concentrations. However, the background of the antifungal effect remains unknown, especially in the case of non-albicans Candida species such as Candida parapsilosis. We examined the effect of tyrosol on growth, adhesion, redox homeostasis, virulence, as well as fluconazole susceptibility. To gain further insights into the physiological consequences of tyrosol treatment, we also determined genome-wide gene expression changes using transcriptome sequencing (RNA-Seq). A concentration of 15 mM tyrosol caused significant growth inhibition within 2 h of the addition of tyrosol, while the adhesion of yeast cells was not affected. Tyrosol increased the production of reactive oxygen species remarkably, as revealed by a dichlorofluorescein test, and it was associated with elevated superoxide dismutase, glutathione peroxidase, and catalase activities. The interaction between fluconazole and tyrosol was antagonistic. Tyrosol exposure resulted in 261 and 181 differentially expressed genes with at least a 1.5-fold increase or decrease in expression, respectively, which were selected for further study. Genes involved in ribosome biogenesis showed downregulation, while genes related to the oxidative stress response and ethanol fermentation were upregulated. In addition, tyrosol treatment upregulated the expression of efflux pump genes, including MDR1 and CDR1, and downregulated the expression of the FAD2 and FAD3 virulence genes involved in desaturated fatty acid formation. Our data demonstrate that exogenous tyrosol significantly affects the physiology and gene expression of C. parapsilosis, which could contribute to the development of treatments targeting quorum sensing in the future. IMPORTANCE Candida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) are key regulators in fungal physiology, which induce phenotypic adaptations, including morphological changes, altered biofilm formation, and synchronized expression of virulence factors. Moreover, they have a remarkable antifungal activity at supraphysiological concentrations. Limited data are available concerning the tyrosol-induced molecular and physiological effects on non-albicans Candida species such as C. parapsilosis. In addition, the background of the previously observed antifungal effect caused by tyrosol remains unknown. This study reveals that tyrosol exposure enhanced the oxidative stress response and the expression of efflux pump genes, while it inhibited growth and ribosome biogenesis as well as several virulence-related genes. Metabolism was changed toward glycolysis and ethanol fermentation. Furthermore, the initial adherence was not influenced significantly in the presence of tyrosol. Our results provide several potential explanations for the previously observed antifungal effect.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Jakab

Tóth

Nagy

et al. 2019

Appl Environ Microbiol

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“…Monteiro et al . () also reported a decrease of around 1 log unit in dual biofilms of C. albicans and C. glabrata , but at 60 mmol l −1 farnesol, a concentration 100 times higher than the one used in this study. A higher potency of farnesol in the present study may be explained by differences in methodology or different susceptibility to farnesol between species.…”

Section: Discussionmentioning

confidence: 40%

“…; Monteiro et al . ). Candida albicans sessile cells also produce farnesol and 2‐phenylethanol, both molecules being associated with modulation of biofilm development (Martins et al .…”

Section: Discussionmentioning

confidence: 97%

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Effect of quorum sensing molecules and natamycin on biofilms of Candida tropicalis and other yeasts isolated from industrial juice filtration membranes

et al. 2019

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Aims Cells limit the cell number of dense biofilms by releasing self‐inhibitory molecules. Here, we aim to assess the effectiveness of yeast quorum sensing (QS) molecules and the antifungal agent natamycin against yeast biofilms of strains commonly isolated from fruit juice ultrafiltration membranes. Methods and Results Yeast QS molecules, such as tyrosol, 2‐phenylethanol and farnesol, were detected by solvent extraction and HS‐SPME GC‐MS in Candida tropicalis cultures. The effect of QS molecules on mono‐ and multispecies biofilms formed by Rhodotorula mucilaginosa, C. tropicalis, Candida krusei and Candida kefyr was evaluated by plate count and epifluorescence microscopy. Farnesol caused a decrease in cell number and disrupted mono‐ and multispecies yeast biofilms during adhesion (0·6 mmol l−1). 2‐phenyl ethanol 1·2 mmol l−1 stimulated biofilm density and increased cell number in both mono‐ and multispecies biofilms, while tyrosol did not show effects when tested against C. tropicalis biofilms (0·05–1·2 mmol l−1). Natamycin caused a strong decrease in cell number and disruption of biofilm structure in C. tropicalis biofilms at high concentrations (0·3–1·2 mmol l−1). The combination of farnesol 0·6 mmol l−1 and natamycin at 0·01 mmol l−1, the maximum concentration of natamycin accepted for direct addition into fruit juices, effectively reduced cell counts and disrupted the structure of C. tropicalis biofilms. Conclusion Farnesol 0·6 mmol l−1 significantly increased the inhibition exerted by natamycin 0·01 mmol l−1 (~5 ppm) reducing biofilm development from juice on stainless steel surfaces. Significance and Impact of the Study These results support the use of QS molecules as biofilm inhibitors in beverages and would certainly inspire the design of novel preservative and cleaning products for the food industry based on combinatory approaches.

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Novel Therapies for Biofilm-Based Candida spp. Infections

Černáková

Light

Salehi

et al. 2019

Advances in Experimental Medicine and Biology

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Antifungal activity of tyrosol and farnesol used in combination against Candida species in the planktonic state or forming biofilms

Abstract: These findings may contribute to the development of oral care products containing tyrosol and farnesol to combat oral infections caused by Candida species.

Cited by 41 publications

References 29 publications

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Physiological and Transcriptional Responses of Candida parapsilosis to Exogenous Tyrosol

Effect of quorum sensing molecules and natamycin on biofilms of Candida tropicalis and other yeasts isolated from industrial juice filtration membranes

Novel Therapies for Biofilm-Based Candida spp. Infections

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