Biomarkers of caspofungin resistance in Candida albicans isolates: A proteomic approach

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.

KEYWORDS:

• Candida albicans
• drug resistance
• caspofungin
• proteomics
• interaction network

Acknowledgments

We would like to acknowledge Dr. Donna MacCallum and Dr. Markus Kostrzewa for providing strains for this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

All proteomic data are available at the PRIDE repository accession number: P×D021283.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2022.2081291.

Author contributions

G.B.D.C. and C.A.M. designed the study. G.B.D.C. conducted the experimental work including characterization of the isolates. G.B.D.C. and D.S. performed the proteomic analysis. A.H. and C.L. performed the differential expression analysis and constructed the interaction network. G.B.D.C. and C.A.M. wrote, reviewed, and edited the manuscript.

Additional information

Funding

The work was supported by the Horizon 2020 [847507]; H2020 Marie Skłodowska-Curie Actions [H2020-MSCA-ITN-2014-642095]; H2020 Marie Skłodowska-Curie Actions [812969].