Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/13957
Title
Adaptation of the emerging pathogenic yeast Candida auris to high caspofungin concentrations correlates with cell wall changes
Author(s)
Lara-Aguilar, Violeta ISCIII | Rueda Hernandez, Maria Cristina ISCIII | Garcia-Barbazan, Irene ISCIII | Varona Fernandez, Sarai ISCIII | Monzon-Fernandez, Sara ISCIII | Jimenez Sancho, Maria Pilar ISCIII | Cuesta de la Plaza, Isabel ISCIII | Zaballos, Angel ISCIII | Zaragoza, Oscar ISCIII
Date issued
2021-12
Citation
Virulence. 2021 Dec;12(1):1400-1417
Language
Inglés
Abstract
Candida auris has emerged as a fungal pathogen that causes nosocomial outbreaks worldwide. Diseases caused by this fungus are of concern, due to its reduced susceptibility to several antifungals. C. auris exhibits paradoxical growth (PG; defined as growth at high, but not intermediate antifungal concentrations) in the presence of caspofungin (CPF). We have characterized the cellular changes associated with adaptation to CPF. Using EUCAST AFST protocols, all C. auris isolates tested showed PG to CPF, although in some isolates it was more prominent. Most isolates also showed a trailing effect (TE) to micafungin and anidulafungin. We identified two FKS genes in C. auris that encode the echinocandins target, namely β-1,3-glucan synthase. FKS1 contained the consensus hot-spot (HS) 1 and HS2 sequences. FKS2 only contained the HS1 region which had a change (F635Y), that has been shown to confer resistance to echinocandins in C. glabrata. PG has been characterized in other species, mainly C. albicans, where high CPF concentrations induced an increase in chitin, cell volume and aggregation. In C. auris CPF only induced a slight accumulation of chitin, and none of the other phenomena. RNAseq experiments demonstrated that CPF induced the expression of genes encoding several GPI-anchored cell wall proteins, membrane proteins required for the stability of the cell wall, chitin synthase and mitogen-activated protein kinases (MAPKs) involved in cell integrity, such as BCK2, HOG1 and MKC1 (SLT2). Our work highlights some of the processes induced in C. auris to adapt to echinocandins.
Subject
Candida auris | FKS | Chitin | Echinocandins | Paradoxical growth or Eagle effect | Resistance | Trailing effect | β-1,3-glucans
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DOI
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