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S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire?
S2.5 RARE YEASTS, SEPTEMBER 21, 2022, 3:00 PM - 4:30 PM: Candida auris (C. auris) is a recently emerged human fungal pathogen of growing concern due to its ability to acquire extensive multidrug resistance (MDR) to all four antifungal drug classes. The unprecedented extent of MDR in C. auris, sugges...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515916/ http://dx.doi.org/10.1093/mmy/myac072.S2.5d |
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author | Carolus, Hans Sofras, Dimitrios Sephton-Clark, Poppy Goossens, Louise Chen, Alicia Pierson, Siebe Romero, Celia Lobo Subotić, Ana Meis, Jacques F. Cuomo, Christina A. Van Dijck, Patrick |
author_facet | Carolus, Hans Sofras, Dimitrios Sephton-Clark, Poppy Goossens, Louise Chen, Alicia Pierson, Siebe Romero, Celia Lobo Subotić, Ana Meis, Jacques F. Cuomo, Christina A. Van Dijck, Patrick |
author_sort | Carolus, Hans |
collection | PubMed |
description | S2.5 RARE YEASTS, SEPTEMBER 21, 2022, 3:00 PM - 4:30 PM: Candida auris (C. auris) is a recently emerged human fungal pathogen of growing concern due to its ability to acquire extensive multidrug resistance (MDR) to all four antifungal drug classes. The unprecedented extent of MDR in C. auris, suggests accelerated resistance evolution, novel mechanisms of resistance, and/or potential fitness compensation. Despite being the first fungus to be officially considered an urgent antimicrobial resistance threat by the CDC (US), insights into the resistance mechanisms and evolutionary dynamics of C. auris are still scarce. : By using high-throughput in vitro experimental evolution with various antifungal drugs, we have obtained a library of resistant strains from four different clades. Through both genome and targeted sequencing, we have discovered novel mutations, especially for polyene resistance, which indicate new mechanisms of resistance and fitness compensation. For the validation of mutations, we have optimized a recyclable CRISPR/Cas9 tool for C. auris based on the C. albicans HIS-FLP system. : By mapping drug susceptibility responses of evolved strains across a library of several antifungals and repurposed drugs, we have discovered trends of cross-resistance and collateral sensitivity. Both phenomena have been extensively studied in tumors and bacteria but remain unexplored in fungi. In the light of these observations, we explore novel treatment schemes that prevent antifungal drug resistance development in C. auris and other pathogenic fungi. |
format | Online Article Text |
id | pubmed-9515916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-95159162022-09-28 S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire? Carolus, Hans Sofras, Dimitrios Sephton-Clark, Poppy Goossens, Louise Chen, Alicia Pierson, Siebe Romero, Celia Lobo Subotić, Ana Meis, Jacques F. Cuomo, Christina A. Van Dijck, Patrick Med Mycol Oral Presentations S2.5 RARE YEASTS, SEPTEMBER 21, 2022, 3:00 PM - 4:30 PM: Candida auris (C. auris) is a recently emerged human fungal pathogen of growing concern due to its ability to acquire extensive multidrug resistance (MDR) to all four antifungal drug classes. The unprecedented extent of MDR in C. auris, suggests accelerated resistance evolution, novel mechanisms of resistance, and/or potential fitness compensation. Despite being the first fungus to be officially considered an urgent antimicrobial resistance threat by the CDC (US), insights into the resistance mechanisms and evolutionary dynamics of C. auris are still scarce. : By using high-throughput in vitro experimental evolution with various antifungal drugs, we have obtained a library of resistant strains from four different clades. Through both genome and targeted sequencing, we have discovered novel mutations, especially for polyene resistance, which indicate new mechanisms of resistance and fitness compensation. For the validation of mutations, we have optimized a recyclable CRISPR/Cas9 tool for C. auris based on the C. albicans HIS-FLP system. : By mapping drug susceptibility responses of evolved strains across a library of several antifungals and repurposed drugs, we have discovered trends of cross-resistance and collateral sensitivity. Both phenomena have been extensively studied in tumors and bacteria but remain unexplored in fungi. In the light of these observations, we explore novel treatment schemes that prevent antifungal drug resistance development in C. auris and other pathogenic fungi. Oxford University Press 2022-09-20 /pmc/articles/PMC9515916/ http://dx.doi.org/10.1093/mmy/myac072.S2.5d Text en © The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Oral Presentations Carolus, Hans Sofras, Dimitrios Sephton-Clark, Poppy Goossens, Louise Chen, Alicia Pierson, Siebe Romero, Celia Lobo Subotić, Ana Meis, Jacques F. Cuomo, Christina A. Van Dijck, Patrick S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire? |
title | S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire? |
title_full | S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire? |
title_fullStr | S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire? |
title_full_unstemmed | S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire? |
title_short | S2.5d Exploring multidrug resistance, fitness compensation, and collateral sensitivity in Candida auris : Fight fire with fire? |
title_sort | s2.5d exploring multidrug resistance, fitness compensation, and collateral sensitivity in candida auris : fight fire with fire? |
topic | Oral Presentations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515916/ http://dx.doi.org/10.1093/mmy/myac072.S2.5d |
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