The possible molecular mechanisms of farnesol on the antifungal resistance of C. albicans biofilms: the regulation of CYR1 and PDE2

Chen, Shengyan; Xia, Jinping; Li, Chengxi; Zuo, Lulu; Wei, Xiaonan

doi:10.1186/s12866-018-1344-z

Cited by 23 publications

(13 citation statements)

References 41 publications

(56 reference statements)

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“…Chen et al (2018) reported that CYR1 and PDE2 regulate resistance mechanisms against various antifungals in C. albicans biofilms. However, farnesol can diminish the resistance of C. albicans biofilms by regulating the expression of the gene CYR1 and PDE2 [ 74 ]. Yu et al (2012) observed that the sterol biosynthetic pathway may contribute to the inhibitory effects of farnesol, as the transcription levels of the ERG11 , ERG25 , ERG6 , ERG3 , and ERG1 genes decreased following farnesol exposure [ 75 ].…”

Section: Farnesolmentioning

confidence: 99%

Fungal Quorum-Sensing Molecules: A Review of Their Antifungal Effect against Candida Biofilms

Kovács

Majoros

2020

JoF

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The number of effective therapeutic strategies against biofilms is limited; development of novel therapies is urgently needed to treat a variety of biofilm-associated infections. Quorum sensing is a special form of microbial cell-to-cell communication that is responsible for the release of numerous extracellular molecules, whose concentration is proportional with cell density. Candida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) have a pivotal role in morphogenesis, biofilm formation, and virulence. Farnesol can mediate the hyphae-to-yeast transition, while tyrosol has the opposite effect of inducing transition from the yeast to hyphal form. A number of questions regarding Candida quorum sensing remain to be addressed; nevertheless, the literature shows that farnesol and tyrosol possess remarkable antifungal and anti-biofilm effect at supraphysiological concentration. Furthermore, previous in vitro and in vivo data suggest that they may have a potent adjuvant effect in combination with certain traditional antifungal agents. This review discusses the most promising farnesol- and tyrosol-based in vitro and in vivo results, which may be a foundation for future development of novel therapeutic strategies to combat Candida biofilms.

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Section: Farnesolmentioning

confidence: 99%

Fungal Quorum-Sensing Molecules: A Review of Their Antifungal Effect against Candida Biofilms

Kovács

Majoros

2020

JoF

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“…They have found that a Candida strain carrying a dominant active variant of Ras 1 , which forms hyphae under non inducing conditions, grew as yeast form in presence of farnesol. A recent report suggested that CYR1 and PDE 2 are involved in the molecular mechanism of farnesol on antifungal resistant to Candida biofilms (Chen et al 2018 ).…”

Section: Response Of Human Fungal Pathogen Candida Albicansmentioning

confidence: 99%

Dual identities for various alcohols in two different yeasts

Chauhan

Karuppayil

2020

Mycology

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Most of the yeast bypasses the developmental stage from simple unicellular yeast to elongated structure like hyphae. Regulation of this transition is governed by various quorum sensing and signalling molecules produced under different conditions of growth, that differ significantly, both physiologically and chemically. The evidence of fungal quorum sensing was uncovered ten years ago after the discovery of farnesol as first eukaryotic quorum sensing molecules in Candida albicans. In addition to farnesol, tyrosol was identified as second quorum sensing molecules in C. albicans controlling physiological activities. After the discovery of farnesol and tyrosol, regulation of morphogenesis through the production of chemical signalling molecules such as isoamyl alcohol, 2-phenylethyl alcohol, 1-dodecanol, E-nerolidol, etc. is reported in C. albicans. Some of the evidence suggests that the budding yeast Saccharomyces cerevisiae exhibits this type of regulation and the signals are regulated by aromatic alcohols which are the end product of amino acid metabolism. The effects of these molecules on morphogenesis are not similar in both yeasts, making comparisons hard. It is hypothesized that these signals works in microorganisms to derive a competitive advantage. Here, we present an example for utilization of competitive strategy by C. albicans and S. cerevisiae over other microorganisms.

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“…The maximum combined effect was dependent on farnesol concentration (Katragkou et al, 2015). Chen et al reported that the resistance of C. albicans biofilms to antifungals is associated with the enzymes CYR1 and PDE2, which are responsible for the synthesis and degradation of the cyclic AMP signaling pathway, and that farnesol reduces the antifungal resistance of C. albicans biofilms (Chen et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Potential antibiofilm activity of farnesol-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles against Candida albicans

Gürsu

2020

J Anal Sci Technol

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Candida species are ubiquitous fungal pathogens and are the most common causes of mucosal and invasive fungal infections in humans. Especially Candida albicans commonly resides as a commensal in the mucosal tissues of approximately half of the human population. When the balance of the normal flora is disrupted or the immune defenses are compromised, Candida species can become pathogenic, often causing recurrent disease in susceptible individuals. The treatments available for Candida infection are commonly drug-based and can involve topical and systemic antifungal agents. However, the use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. Candida species ability to produce drug-resistant biofilm is an important factor in human infections, because microorganisms within biofilm benefit from various advantages over their planktonic counterparts including protection from antimicrobials and chemicals. These limitations emphasize the need to develop new and more effective antifungal agents. Natural products are attractive alternatives for this purpose due to their broad spectrum of biological activities. Farnesol is produced by many microorganisms and found in some essential oils. It has also a great attention as a quorum-sensing molecule and virulence factor. It has also antimicrobial potential due to its inhibitory effects on various bacteria and fungi. However, as it is a hydrophobic component, its solubility and biofilm inhibiting properties are limited. To overcome these shortcomings, nanoparticle-based drug delivery systems have been successfully used. For this purpose, especially using biodegradable polymeric nanoparticles has gained increasing attention owing to their biocompatibility and minimal toxicity. Poly (DL-lactide-co-glycolide) (PLGA) is the most widely used polymer in this area. In this study, farnesol is loaded to PLGA nanoparticles (F-PLGA NPs) by emulsion evaporation method and characterized by DLS, TEM, and FT-IR analyses. Our TEM findings indicate that the sizes of F-PLGA NPs are approximately 140 nm. The effects of F-PLGA NPs on planktonic cells and biofilm formation of C. albicans were compared with effects of farnesol alone. Farnesol inhibits the growth at a range of 53% at a concentration of 2.5 μL compared to the control group. This rate is 45% for F-PLGA NPs at the same concentration. However, although farnesol amount in F-PLGA is approximately 22.5% of the total volume, the observed effect is significant. In TEM examinations, planktonic Candida cells treated with farnesol showed relatively regular ultrastructural morphology. Few membrane and wall damage and electron density in the cytoplasm were determined. In F-PLGA NP-treated cells, increased irregular cell morphology, membrane and wall damages, and large vacuoles are observed. Our SEM and XTT data suggest that F-PLGA NPs can reduce the biofilm formation at lower concentrations than farnesol alone 57%, and our results showed that F-PLGA NPs are effective and biocompatible alternatives for inhibiting growth and biofilm formation of C. albicans, but detailed studies are needed.

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The possible molecular mechanisms of farnesol on the antifungal resistance of C. albicans biofilms: the regulation of CYR1 and PDE2

Cited by 23 publications

References 41 publications

Fungal Quorum-Sensing Molecules: A Review of Their Antifungal Effect against Candida Biofilms

Fungal Quorum-Sensing Molecules: A Review of Their Antifungal Effect against Candida Biofilms

Dual identities for various alcohols in two different yeasts

Potential antibiofilm activity of farnesol-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles against Candida albicans

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