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Published on: April 2, 2021
Biomarkers of caspofungin resistance in Candida albicans isolates: A proteomic approach
Giuseppe Buda De Cesare1, Ahmed Hafez2,3,4, David Stead5
1School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, UK.
Abstract:
Candida albicans is a clinically important polymorphic fungal pathogen that causes life-threatening invasive infections in immunocompromised patients. Antifungal therapy failure is a substantial clinical problem, due to the emergence of an increasing number of drug-resistant isolates. Caspofungin is a common antifungal drug, often used as first-line therapy that inhibits cell wall β-(1,3)-glucan synthesis. In this work, the cell surface of different echinocandin-resistant C. albicans clinical isolates was compared with sensitive isolates and their responses to echinocandin treatment analyzed. Proteomic analysis detected changes in the repertoire of proteins involved in cell wall organization and maintenance, in drug-resistant strains compared to susceptible isolates and after incubation with caspofungin. Moreover, an interaction network was created from the differential expression results. Our findings suggest drug resistance may involve not only a different cell wall architecture, but also a different response to drugs.
Insights
Drug-resistant Candida albicans exhibits altered cell surface proteins and responses to echinocandin treatment. This suggests that resistance mechanisms involve changes in cell wall structure and drug interaction.
Area of Science:
- Mycology
- Infectious Diseases
- Drug Resistance
Background:
- Candida albicans is a major cause of invasive fungal infections, particularly in immunocompromised individuals.
- Antifungal drug resistance in C. albicans is a growing clinical challenge, leading to treatment failures.
- Caspofungin, an echinocandin, is a first-line antifungal targeting fungal cell wall synthesis.
Purpose of the Study:
- To compare the cell surface proteome of echinocandin-resistant C. albicans clinical isolates with susceptible ones.
- To analyze the response of resistant and susceptible C. albicans to echinocandin treatment.
- To identify potential mechanisms underlying echinocandin resistance in C. albicans.
Main Methods:
- Comparative proteomic analysis of cell surface proteins from resistant and susceptible C. albicans isolates.
- Assessment of isolate responses to caspofungin treatment.
- Construction of protein-protein interaction networks based on differential expression data.
Main Results:
- Proteomic analysis revealed significant changes in cell wall organization and maintenance proteins in resistant C. albicans strains.
- Differential protein expression was observed in resistant strains compared to susceptible isolates, both at baseline and after caspofungin exposure.
- An interaction network highlighted key protein changes associated with drug resistance.
Conclusions:
- Echinocandin resistance in C. albicans may involve alterations in cell wall architecture.
- The response to echinocandin treatment differs between resistant and susceptible C. albicans isolates.
- Understanding these changes can inform strategies to combat antifungal drug resistance.
