REAL

Acquired Triazole Resistance Alters Pathogenicity-Associated Features in Candida auris in an Isolate-Dependent Manner

Bohner, Flóra and Papp, Csaba Gergő and Takács, Tamás and Varga, Mónika and Szekeres, András and Nosanchuk, Joshua D. and Vágvölgyi, Csaba and Tóth, Renáta and Gácser, Attila (2023) Acquired Triazole Resistance Alters Pathogenicity-Associated Features in Candida auris in an Isolate-Dependent Manner. JOURNAL OF FUNGI, 9 (12). ISSN 2309-608X

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Abstract

Fluconazole resistance is commonly encountered in Candida auris, and the yeast frequently displays resistance to other standard drugs, which severely limits the number of effective therapeutic agents against this emerging pathogen. In this study, we aimed to investigate the effect of acquired azole resistance on the viability, stress response, and virulence of this species. Fluconazole-, posaconazole-, and voriconazole- resistant strains were generated from two susceptible C. auris clinical isolates (0381, 0387) and compared under various conditions. Several evolved strains became pan-azole-resistant, as well as echinocandin-cross-resistant. While being pan-azole-resistant, the 0381-derived posaconazole-evolved strain colonized brain tissue more efficiently than any other strain, suggesting that fitness cost is not necessarily a consequence of resistance development in C. auris. All 0387-derived evolved strains carried a loss of function mutation (R160S) in BCY1, an inhibitor of the PKA pathway. Sequencing data also revealed that posaconazole treatment can result in ERG3 mutation in C. auris. Despite using the same mechanisms to generate the evolved strains, both genotype and phenotype analysis highlighted that the development of resistance was unique for each strain. Our data suggest that C. auris triazole resistance development is a highly complex process, initiated by several pleiotropic factors.

Item Type: Article
Uncontrolled Keywords: C. auris; antifungal resistance; triazoles; microevolution; virulence
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 02 Apr 2024 09:32
Last Modified: 02 Apr 2024 09:32
URI: https://real.mtak.hu/id/eprint/191374

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