Abstract
The high virulence of Candida auris, a pathogen fungus considered as a global threat for public health, is due to its peculiar traits such as its intrinsic resistance to conventional antifungals. Its biofilm lifestyle certainly promotes the prolonged survival of C. auris after disinfection or antifungal treatments. In this work, for the first time, we detected persister cells in a biofilm of C. auris in a microwell plate model, following caspofungin treatment. Furthermore, we showed how persisters can progressively develop a new biofilm in situ, mimicking the re-colonization of a surface which may be responsible for recalcitrant infections. Plant-derived compounds, such as essential oils, may represent a valid alternative to combat fungal infections. Here, Lavandula angustifolia essential oil, as free or encapsulated in liposomes, was used to eradicate primary and persister-derived biofilms of C. auris, confirming the great potential of alternative compounds against emergent fungal pathogens. As in other Candida species, the action of essential oils against C. auris involves ROS production and affects the expression of some biofilm-related genes.
Highlights
Since its discovery in 2009 [1], the pathogenic yeast Candida auris has elicited several worldwide outbreaks; it is considered as a global threat to public health, with an estimated mortality range from 28% to 66%
In our study, the gene related to ergosterol biosynthesis, ERG11, was downregulated during eradication with liposome encapsulated oil, and this effect could be attributed to its cell membrane-targeting activity, while we could observe a significant increase in expression of the ERG11 gene when the selected L. angustifolia oil were applied to persister-derived biofilm
The liposomes were prepared at a total lipid concentration of 0.1 mM, mixed aggregates of PC, Chol and L. angustifolia oil were dissolved in chloroform and subsequently the solvent was evaporated under a stream of nitrogen gas
Summary
Since its discovery in 2009 [1], the pathogenic yeast Candida auris has elicited several worldwide outbreaks; it is considered as a global threat to public health, with an estimated mortality range from 28% to 66%. Even if plant-derived compounds have become an important potential for counteracting therapeutic failures in the treatment of fungal infections, literature data on their action against emerging yeast pathogens are still limited [17]. The potential of both bark and leaf Cinnamomum zeylanicum EOs to exert antifungal activity against C. auris has been reported, showing their ability to damage the membrane structures of fungal cells [18], but the treatment of persistent infections remains a challenge, and the activity of EOs against C. auris biofilm has not yet been studied. Some insights into the working mechanisms of action of both free and encapsulated oil on C. auris cells in the persister-derived biofilm were provided, by analysing the analysing the redox status and the transcriptional expression of genes (ALS5, CDR1, ERG11, HOG1)
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