Farnesol increases the activity of echinocandins against Candida auris biofilms

Nagy, Fruzsina; Tóth, Zoltán; Daróczi, Lajos; Székely, Adrien; Borman, Andrew M.; Majoros, László; Kovács, Renátó

doi:10.1093/mmy/myz057

Cited by 38 publications

(66 citation statements)

References 21 publications

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“…Fernández-Rivero et al (2017) reported that a supraphysiological farnesol concentration (300 μM) improved the activity of amphotericin B against Candida tropicalis biofilms but did not affect anidulafungin [ 77 ]. Two recent studies by Nagy et al concluded that farnesol significantly enhanced the activity of echinocandins and triazoles against one-day-old C. auris biofilms in vitro, suggesting an alternative approach to overcome the previously well-documented azole and echinocandin resistance of C. auris biofilms [ 45 , 78 ].…”

Section: Farnesolmentioning

confidence: 99%

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

Kovács

Majoros

2020

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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

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“…Similarly, combinations of azoles with geldamycin were indifferent against the same strains [53]. Furthermore, Nagy and colleagues [55] reported that combinations of farnesol and the three echinocandins approved by the F.D.A. showed positive results against biofilms of C. auris.…”

Section: Alternative Therapies and Clinical Applicabilitymentioning

confidence: 97%

“…Farnesol is a sesquiterpene alcohol quorum-sensing molecule, which works to prevent the formation of C. albicans biofilms. This drug works by inhibiting the support cascade Ras1-cAMP-PKA that acts at the hypha-to-yeast transition [55][56][57]. The synergism mechanism of these drugs is not completely understood; however, farnesol is believed to modulate the expression of genes linked to ergosterol biosynthesis [58].…”

Section: Alternative Therapies and Clinical Applicabilitymentioning

confidence: 99%

“…The synergism mechanism of these drugs is not completely understood; however, farnesol is believed to modulate the expression of genes linked to ergosterol biosynthesis [58]. Thus, deleterious effects on the cell wall caused by echinocandins added to the imbalance in the ergosterol synthesis modulated by farnesol, can act simultaneously, causing fungal cell wall and membrane damage [55]. Besides, farnesol can induce the production of reactive oxygen species and disruption of mithocondrial functions, which can lead to enhanced echinocandin activity [58].…”

Section: Alternative Therapies and Clinical Applicabilitymentioning

confidence: 99%

“…However, they can be used as an adjuvant in the action of echinocandins in therapies of local action (lock therapy). For biofilm treatment, this strategy avoids the toxic effect, since farnesol acts only within a catheter [55,57,60].…”

Section: Alternative Therapies and Clinical Applicabilitymentioning

confidence: 99%

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Echinocandins as Biotechnological Tools for Treating Candida auris Infections

Cândido

Affonseca

Cardoso

et al. 2020

JoF

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Candida auris has been reported in the past few years as an invasive fungal pathogen of high interest. Its recent emergence in healthcare-associated infections triggered the efforts of researchers worldwide, seeking additional alternatives to the use of traditional antifungals such as azoles. Lipopeptides, specially the echinocandins, have been reported as an effective approach to control pathogenic fungi. However, despite its efficiency against C. auris, some isolates presented echinocandin resistance. Thus, therapies focused on echinocandins’ synergism with other antifungal drugs were widely explored, representing a novel possibility for the treatment of C. auris infections.

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