Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis

Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis i...

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Main Authors:	Quinto-Alemany, David, Canerina-Amaro, Ana, Hernández-Abad, Luís G., Machín, Félix, Romesberg, Floyd E., Gil-Lamaignere, Cristina
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409178/

id	pubmed-3409178
recordtype	oai_dc
spelling	pubmed-34091782012-08-02 Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis Quinto-Alemany, David Canerina-Amaro, Ana Hernández-Abad, Luís G. Machín, Félix Romesberg, Floyd E. Gil-Lamaignere, Cristina Research Article Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms) would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP), giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM) experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae –5-FC), 600 (C. albicans –5-FC) or 1000 (S. cerevisiae – CSP) fold higher than the spontaneous mutation frequency, the experimental data for C. albicans –5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae –5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously. Public Library of Science 2012-07-31 /pmc/articles/PMC3409178/ /pubmed/22860105 http://dx.doi.org/10.1371/journal.pone.0042279 Text en © 2012 Quinto-Alemany et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Quinto-Alemany, David Canerina-Amaro, Ana Hernández-Abad, Luís G. Machín, Félix Romesberg, Floyd E. Gil-Lamaignere, Cristina
spellingShingle	Quinto-Alemany, David Canerina-Amaro, Ana Hernández-Abad, Luís G. Machín, Félix Romesberg, Floyd E. Gil-Lamaignere, Cristina Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis
author_facet	Quinto-Alemany, David Canerina-Amaro, Ana Hernández-Abad, Luís G. Machín, Félix Romesberg, Floyd E. Gil-Lamaignere, Cristina
author_sort	Quinto-Alemany, David
title	Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis
title_short	Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis
title_full	Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis
title_fullStr	Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis
title_full_unstemmed	Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis
title_sort	yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis
description	Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms) would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP), giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM) experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae –5-FC), 600 (C. albicans –5-FC) or 1000 (S. cerevisiae – CSP) fold higher than the spontaneous mutation frequency, the experimental data for C. albicans –5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae –5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409178/
_version_	1611546770823708672

Yeasts Acquire Resistance Secondary to Antifungal Drug Treatment by Adaptive Mutagenesis

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