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Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms

Candida albicans is one of the most common causes of hospital-acquired urinary tract infections (UTIs). However, azoles are poorly active against biofilms, echinocandins do not achieve clinically useful urinary concentrations, and amphotericin B exhibits severe toxicities. Thus, novel strategies are...

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Autores principales: Sundararajan, Anitha, Rane, Hallie S., Ramaraj, Thiruvarangan, Sena, Johnny, Howell, Amy B., Bernardo, Stella M., Schilkey, Faye D., Lee, Samuel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082538/
https://www.ncbi.nlm.nih.gov/pubmed/30089157
http://dx.doi.org/10.1371/journal.pone.0201969
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author Sundararajan, Anitha
Rane, Hallie S.
Ramaraj, Thiruvarangan
Sena, Johnny
Howell, Amy B.
Bernardo, Stella M.
Schilkey, Faye D.
Lee, Samuel A.
author_facet Sundararajan, Anitha
Rane, Hallie S.
Ramaraj, Thiruvarangan
Sena, Johnny
Howell, Amy B.
Bernardo, Stella M.
Schilkey, Faye D.
Lee, Samuel A.
author_sort Sundararajan, Anitha
collection PubMed
description Candida albicans is one of the most common causes of hospital-acquired urinary tract infections (UTIs). However, azoles are poorly active against biofilms, echinocandins do not achieve clinically useful urinary concentrations, and amphotericin B exhibits severe toxicities. Thus, novel strategies are needed to prevent Candida UTIs, which are often associated with urinary catheter biofilms. We previously demonstrated that cranberry-derived proanthocyanidins (PACs) prevent C. albicans biofilm formation in an in vitro urinary model. To elucidate functional pathways unique to urinary biofilm development and PAC inhibition, we investigated the transcriptome of C. albicans in artificial urine (AU), with and without PACs. C. albicans biofilm and planktonic cells were cultivated with or without PACs. Genome-wide expression analysis was performed by RNA sequencing. Differentially expressed genes were determined using DESeq2 software; pathway analysis was performed using Cytoscape. Approximately 2,341 of 6,444 total genes were significantly expressed in biofilm relative to planktonic cells. Functional pathway analysis revealed that genes involved in filamentation, adhesion, drug response and transport were up-regulated in urinary biofilms. Genes involved in carbon and nitrogen metabolism and nutrient response were down-regulated. In PAC-treated urinary biofilms compared to untreated control biofilms, 557 of 6,444 genes had significant changes in gene expression. Genes downregulated in PAC-treated biofilms were implicated in iron starvation and adhesion pathways. Although urinary biofilms share key features with biofilms formed in other environments, many genes are uniquely expressed in urinary biofilms. Cranberry-derived PACs interfere with the expression of iron acquisition and adhesion genes within urinary biofilms.
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spelling pubmed-60825382018-08-28 Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms Sundararajan, Anitha Rane, Hallie S. Ramaraj, Thiruvarangan Sena, Johnny Howell, Amy B. Bernardo, Stella M. Schilkey, Faye D. Lee, Samuel A. PLoS One Research Article Candida albicans is one of the most common causes of hospital-acquired urinary tract infections (UTIs). However, azoles are poorly active against biofilms, echinocandins do not achieve clinically useful urinary concentrations, and amphotericin B exhibits severe toxicities. Thus, novel strategies are needed to prevent Candida UTIs, which are often associated with urinary catheter biofilms. We previously demonstrated that cranberry-derived proanthocyanidins (PACs) prevent C. albicans biofilm formation in an in vitro urinary model. To elucidate functional pathways unique to urinary biofilm development and PAC inhibition, we investigated the transcriptome of C. albicans in artificial urine (AU), with and without PACs. C. albicans biofilm and planktonic cells were cultivated with or without PACs. Genome-wide expression analysis was performed by RNA sequencing. Differentially expressed genes were determined using DESeq2 software; pathway analysis was performed using Cytoscape. Approximately 2,341 of 6,444 total genes were significantly expressed in biofilm relative to planktonic cells. Functional pathway analysis revealed that genes involved in filamentation, adhesion, drug response and transport were up-regulated in urinary biofilms. Genes involved in carbon and nitrogen metabolism and nutrient response were down-regulated. In PAC-treated urinary biofilms compared to untreated control biofilms, 557 of 6,444 genes had significant changes in gene expression. Genes downregulated in PAC-treated biofilms were implicated in iron starvation and adhesion pathways. Although urinary biofilms share key features with biofilms formed in other environments, many genes are uniquely expressed in urinary biofilms. Cranberry-derived PACs interfere with the expression of iron acquisition and adhesion genes within urinary biofilms. Public Library of Science 2018-08-08 /pmc/articles/PMC6082538/ /pubmed/30089157 http://dx.doi.org/10.1371/journal.pone.0201969 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Sundararajan, Anitha
Rane, Hallie S.
Ramaraj, Thiruvarangan
Sena, Johnny
Howell, Amy B.
Bernardo, Stella M.
Schilkey, Faye D.
Lee, Samuel A.
Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms
title Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms
title_full Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms
title_fullStr Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms
title_full_unstemmed Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms
title_short Cranberry-derived proanthocyanidins induce a differential transcriptomic response within Candida albicans urinary biofilms
title_sort cranberry-derived proanthocyanidins induce a differential transcriptomic response within candida albicans urinary biofilms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082538/
https://www.ncbi.nlm.nih.gov/pubmed/30089157
http://dx.doi.org/10.1371/journal.pone.0201969
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