Long-term stability of acquired drug resistance and resistance associated mutations in the fungal pathogen Nakaseomyces glabratus ( Candida glabrata ).

Autor:	Ksiezopolska E; Department of Life Sciences, Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain.; Department of Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain., Schikora-Tamarit MÀ; Department of Life Sciences, Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain.; Department of Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain., Carlos Nunez-Rodriguez J; Department of Life Sciences, Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain.; Department of Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain., Gabaldón T; Department of Life Sciences, Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain.; Department of Mechanisms of Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.; Department of CIBERinfect, Centro Investigación Biomédica En Red de Enfermedades Infecciosas, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2024 Jul 15; Vol. 14, pp. 1416509. Date of Electronic Publication: 2024 Jul 15 (Print Publication: 2024).
DOI:	10.3389/fcimb.2024.1416509
Abstrakt:	The limited number of available antifungal drugs and the increasing number of fungal isolates that show drug or multidrug resistance pose a serious medical threat. Several yeast pathogens, such as Nakaseomyces glabratus ( Candida glabrata ), show a remarkable ability to develop drug resistance during treatment through the acquisition of genetic mutations. However, how stable this resistance and the underlying mutations are in non-selective conditions remains poorly characterized. The stability of acquired drug resistance has fundamental implications for our understanding of the appearance and spread of drug-resistant outbreaks and for defining efficient strategies to combat them. Here, we used an in vitro evolution approach to assess the stability under optimal growth conditions of resistance phenotypes and resistance-associated mutations that were previously acquired under exposure to antifungals. Our results reveal a remarkable stability of the resistant phenotype and the underlying mutations in a significant number of evolved populations, which conserved their phenotype for at least two months in the absence of drug-selective pressure. We observed a higher stability of anidulafungin resistance over fluconazole resistance, and of resistance-conferring point mutations as compared with aneuploidies. In addition, we detected accumulation of novel mutations in previously altered resistance-associated genes in non-selective conditions, which suggest a possible compensatory role. We conclude that acquired resistance, particularly to anidulafungin, is a long-lasting phenotype, which has important implications for the persistence and propagation of drug-resistant clinical outbreaks. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Ksiezopolska, Schikora-Tamarit, Carlos Nunez-Rodriguez and Gabaldón.)
Databáze:	MEDLINE
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