Biomarkers of caspofungin resistance in isolates: A proteomic approach.

Giuseppe Buda De Cesare, Ahmed Hafez, David Stead, Carlos Llorens, Carol A Munro

Journal: Virulence 2022;13(1):1005-1018

PMID: 35730400

Abstract

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 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.

Address: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, UK.; Biotechvana, Parc Científic Universitat de València, Valencia, Spain.; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.; Faculty of Computer and Information, Minia University, Minia, Egypt.; Aberdeen Proteomics, Rowett Institute ofNutrition and Health, University of Aberdeen, Foresterhill, UK.
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