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Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance

Candida auris has emerged as an outbreak pathogen associated with high mortality. Biofilm formation and linked drug resistance are common among Candida species. Drug sequestration by the biofilm matrix accounts for much of the antifungal tolerance. In this study, we examine the biofilm matrix compos...

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Autores principales: Dominguez, E. G., Zarnowski, R., Choy, H. L., Zhao, M., Sanchez, H., Nett, Jeniel E., Andes, D. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315084/
https://www.ncbi.nlm.nih.gov/pubmed/30602527
http://dx.doi.org/10.1128/mSphereDirect.00680-18
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author Dominguez, E. G.
Zarnowski, R.
Choy, H. L.
Zhao, M.
Sanchez, H.
Nett, Jeniel E.
Andes, D. R.
author_facet Dominguez, E. G.
Zarnowski, R.
Choy, H. L.
Zhao, M.
Sanchez, H.
Nett, Jeniel E.
Andes, D. R.
author_sort Dominguez, E. G.
collection PubMed
description Candida auris has emerged as an outbreak pathogen associated with high mortality. Biofilm formation and linked drug resistance are common among Candida species. Drug sequestration by the biofilm matrix accounts for much of the antifungal tolerance. In this study, we examine the biofilm matrix composition and function for a diverse set of C. auris isolates. We show that matrix sequesters nearly 70% of the available triazole antifungal. Like the biofilms formed by other Candida spp., we find that the matrix of C. auris is rich in mannan-glucan polysaccharides and demonstrate that their hydrolysis reduces drug tolerance. This biofilm matrix resistance mechanism appears conserved among Candida species, including C. auris. IMPORTANCE Candida auris is an emerging fungal threat linked to poor patient outcomes. The factors responsible for this apparent increase in pathogenicity remain largely unknown. Biofilm formation has been suggested as an important factor for persistence of this organism in patients and the environment. Our findings reveal one mechanism utilized by C. auris to evade the effect of triazole antifungal therapy during biofilm growth. The conservation of the protective biofilm matrix among Candida spp. suggests that is a promising pan-fungal Candida biofilm drug target.
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spelling pubmed-63150842019-01-11 Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance Dominguez, E. G. Zarnowski, R. Choy, H. L. Zhao, M. Sanchez, H. Nett, Jeniel E. Andes, D. R. mSphere Research Article Candida auris has emerged as an outbreak pathogen associated with high mortality. Biofilm formation and linked drug resistance are common among Candida species. Drug sequestration by the biofilm matrix accounts for much of the antifungal tolerance. In this study, we examine the biofilm matrix composition and function for a diverse set of C. auris isolates. We show that matrix sequesters nearly 70% of the available triazole antifungal. Like the biofilms formed by other Candida spp., we find that the matrix of C. auris is rich in mannan-glucan polysaccharides and demonstrate that their hydrolysis reduces drug tolerance. This biofilm matrix resistance mechanism appears conserved among Candida species, including C. auris. IMPORTANCE Candida auris is an emerging fungal threat linked to poor patient outcomes. The factors responsible for this apparent increase in pathogenicity remain largely unknown. Biofilm formation has been suggested as an important factor for persistence of this organism in patients and the environment. Our findings reveal one mechanism utilized by C. auris to evade the effect of triazole antifungal therapy during biofilm growth. The conservation of the protective biofilm matrix among Candida spp. suggests that is a promising pan-fungal Candida biofilm drug target. American Society for Microbiology 2019-01-02 /pmc/articles/PMC6315084/ /pubmed/30602527 http://dx.doi.org/10.1128/mSphereDirect.00680-18 Text en Copyright © 2019 Dominguez et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Dominguez, E. G.
Zarnowski, R.
Choy, H. L.
Zhao, M.
Sanchez, H.
Nett, Jeniel E.
Andes, D. R.
Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance
title Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance
title_full Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance
title_fullStr Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance
title_full_unstemmed Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance
title_short Conserved Role for Biofilm Matrix Polysaccharides in Candida auris Drug Resistance
title_sort conserved role for biofilm matrix polysaccharides in candida auris drug resistance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315084/
https://www.ncbi.nlm.nih.gov/pubmed/30602527
http://dx.doi.org/10.1128/mSphereDirect.00680-18
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