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Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4

Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new ag...

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Autores principales: Bing, Jian, Guan, Zhangyue, Zheng, Tianhong, Zhang, Zhijie, Fan, Shuru, Ennis, Craig L., Nobile, Clarissa J., Huang, Guanghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035925/
https://www.ncbi.nlm.nih.gov/pubmed/36913408
http://dx.doi.org/10.1371/journal.ppat.1011239
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author Bing, Jian
Guan, Zhangyue
Zheng, Tianhong
Zhang, Zhijie
Fan, Shuru
Ennis, Craig L.
Nobile, Clarissa J.
Huang, Guanghua
author_facet Bing, Jian
Guan, Zhangyue
Zheng, Tianhong
Zhang, Zhijie
Fan, Shuru
Ennis, Craig L.
Nobile, Clarissa J.
Huang, Guanghua
author_sort Bing, Jian
collection PubMed
description Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new aggregating form of two clinical C. auris isolates with increased biofilm forming capacity due to enhanced adherence of adjacent cells and surfaces. Unlike the previously reported aggregating morphology, this new aggregating multicellular form of C. auris can become unicellular after treatment with proteinase K or trypsin. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain’s enhanced adherence and biofilm forming capacities. Many clinical isolates of C. auris have variable copy numbers of ALS4, suggesting that this subtelomeric region exhibits instability. Global transcriptional profiling and quantitative real-time PCR assays indicated that genomic amplification of ALS4 results in a dramatic increase in overall levels of transcription. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains of C. auris, this new Als4-mediated aggregative-form strain of C. auris displays several unique characteristics in terms of its biofilm formation, surface colonization, and virulence.
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spelling pubmed-100359252023-03-24 Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4 Bing, Jian Guan, Zhangyue Zheng, Tianhong Zhang, Zhijie Fan, Shuru Ennis, Craig L. Nobile, Clarissa J. Huang, Guanghua PLoS Pathog Research Article Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new aggregating form of two clinical C. auris isolates with increased biofilm forming capacity due to enhanced adherence of adjacent cells and surfaces. Unlike the previously reported aggregating morphology, this new aggregating multicellular form of C. auris can become unicellular after treatment with proteinase K or trypsin. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain’s enhanced adherence and biofilm forming capacities. Many clinical isolates of C. auris have variable copy numbers of ALS4, suggesting that this subtelomeric region exhibits instability. Global transcriptional profiling and quantitative real-time PCR assays indicated that genomic amplification of ALS4 results in a dramatic increase in overall levels of transcription. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains of C. auris, this new Als4-mediated aggregative-form strain of C. auris displays several unique characteristics in terms of its biofilm formation, surface colonization, and virulence. Public Library of Science 2023-03-13 /pmc/articles/PMC10035925/ /pubmed/36913408 http://dx.doi.org/10.1371/journal.ppat.1011239 Text en © 2023 Bing et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bing, Jian
Guan, Zhangyue
Zheng, Tianhong
Zhang, Zhijie
Fan, Shuru
Ennis, Craig L.
Nobile, Clarissa J.
Huang, Guanghua
Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4
title Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4
title_full Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4
title_fullStr Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4
title_full_unstemmed Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4
title_short Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4
title_sort clinical isolates of candida auris with enhanced adherence and biofilm formation due to genomic amplification of als4
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035925/
https://www.ncbi.nlm.nih.gov/pubmed/36913408
http://dx.doi.org/10.1371/journal.ppat.1011239
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