Related Experiment Video
Updated: Oct 17, 2025
Automation of Bio-Atomic Force Microscope Measurements on Hundreds of C. albicans Cells
Published on: April 2, 2021
Caspofungin-resistance in Candida auris is cell wall-dependent phenotype and potential prevention by zinc oxide
Bahgat Fayed1,2, Manju Nidagodu Jayakumar1, Sameh S M Soliman1,3
1Research Institute for Medical and Health sciences, University of Sharjah, P.O. Box 27272, Sharjah, UAE.
Abstract:
Candida auris is an emergent nosocomial multi-drug-resistant yeast that represents a global health threat. Recently, C. auris clinical isolates with caspofungin resistance were identified. Mutation in FKS1 gene was determined as a mechanism of resistance. However, the ability of C. auris to develop acquired and cross-resistance has never been investigated. Herein, this resistance ability due to caspofungin and associate mechanisms were investigated. C. auris clinical isolate was successively cultured for ten generations in the presence of caspofungin compared to fluconazole-treatment and untreated controls. This was followed by the analysis of target gene expression and phenotypic changes. The obtained results showed that caspofungin-treated C. auris exhibited elevated MIC50(caspofungin), slower growth, elevated chitin content, overexpression of caspofungin target genes, and cross-resistance to fluconazole. Interestingly, caspofungin exposure induced cell-cell adhesion and biofilm formation. C. auris gradually lost caspofungin resistance after removal of antifungal pressure, while keeping the overexpression of fungal cell wall-related genes including ALS5. We propose that C. auris ageing in the presence of caspofungin caused the development of persistent phenotypic changes in the fungal cell wall, leading to acquired and physical cross-resistance mechanisms. Surprisingly, formulation of caspofungin in zinc oxide nanoparticles prevented the aforementioned behavioral changes regardless of the pathogen generations.
Lay Summary:
Candida auris developed resistance against caspofungin. Our data indicated that this resistance mechanism is unique because of changes in the genes related to cell wall adhesions. Formulation of caspofungin in ZnO nanoparticles was able to overcome these phenotypic changes.
Insights
Candida auris developed caspofungin resistance through cell wall changes, leading to fluconazole cross-resistance. Zinc oxide nanoparticles prevented these resistance mechanisms, offering a potential therapeutic strategy against this global health threat.
Area of Science:
- Mycology
- Antimicrobial Resistance
- Nanotechnology
Background:
- Candida auris is a multidrug-resistant yeast causing global health concerns.
- Emerging caspofungin resistance in C. auris is linked to FKS1 gene mutations.
- The development of acquired and cross-resistance in C. auris remains poorly understood.
Purpose of the Study:
- To investigate the development of acquired and cross-resistance in Candida auris upon caspofungin exposure.
- To analyze the underlying genetic and phenotypic changes associated with caspofungin resistance.
- To evaluate the efficacy of zinc oxide nanoparticles in preventing caspofungin resistance.
Main Methods:
- Serial culturing of C. auris in the presence of caspofungin for ten generations.
- Analysis of target gene expression and phenotypic alterations.
- Assessment of antifungal susceptibility and biofilm formation.
Main Results:
- Caspofungin-treated C. auris showed increased resistance, slower growth, and elevated chitin content.
- Overexpression of caspofungin target genes and cross-resistance to fluconazole were observed.
- Caspofungin exposure induced cell-cell adhesion, biofilm formation, and persistent cell wall changes.
Conclusions:
- Prolonged caspofungin exposure induces acquired and cross-resistance in C. auris via persistent fungal cell wall modifications.
- Zinc oxide nanoparticle formulation of caspofungin effectively prevented resistance development.
- These findings highlight novel resistance mechanisms and a potential strategy to combat C. auris infections.
