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Updated: Oct 31, 2025
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Published on: April 2, 2021
Adaptation of the emerging pathogenic yeast Candida auris to high caspofungin concentrations correlates with cell
Violeta Lara-Aguilar1, Cristina Rueda1, Irene García-Barbazán1
1Mycology Reference Laboratory, National Centre for Microbiology, Instituto De Salud Carlos III, Madrid, Spain.
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.
Insights
Candida auris shows paradoxical growth with caspofungin, adapting through cell wall changes and specific gene expression. This study details its resistance mechanisms to echinocandin antifungals.
Area of Science:
- Mycology
- Antimicrobial Resistance
- Fungal Pathogenesis
Background:
- Candida auris is a global nosocomial pathogen with reduced susceptibility to antifungals.
- Paradoxical growth (PG) is observed with caspofungin (CPF) in C. auris.
- Echinocandins target beta-1,3-glucan synthase, crucial for fungal cell wall integrity.
Purpose of the Study:
- To characterize cellular adaptations of C. auris to caspofungin (CPF).
- To investigate the genetic basis of paradoxical growth (PG) and trailing effect (TE) in C. auris.
- To identify molecular mechanisms underlying C. auris adaptation to echinocandins.
Main Methods:
- Phenotypic characterization of C. auris isolates using EUCAST AFST protocols.
- Genetic analysis of FKS genes (FKS1 and FKS2) in C. auris.
- RNA sequencing (RNAseq) to analyze gene expression changes induced by CPF.
Main Results:
- All C. auris isolates exhibited PG to CPF, with varying prominence.
- A specific FKS2 mutation (F635Y) was identified, potentially conferring resistance.
- CPF induced chitin accumulation and altered expression of cell wall and cell integrity genes (GPI-anchored proteins, chitin synthase, MAPKs).
Conclusions:
- C. auris adapts to echinocandins through specific cellular and molecular responses.
- FKS gene variations may contribute to antifungal resistance in C. auris.
- Understanding these adaptation mechanisms is crucial for managing C. auris infections.
