The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid

Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal (GI) microbiota were shown to keep C. a...

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Main Authors: Fabien Cottier, Alrina Shin Min Tan, Marina Yurieva, Webber Liao, Josephine Lum, Michael Poidinger, Francesca Zolezzi, Norman Pavelka
Format: Article
Language:English
Published: Oxford University Press 2017-11-01
Series:G3: Genes, Genomes, Genetics
Subjects:
Online Access:http://g3journal.org/lookup/doi/10.1534/g3.117.300238
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author Fabien Cottier
Alrina Shin Min Tan
Marina Yurieva
Webber Liao
Josephine Lum
Michael Poidinger
Francesca Zolezzi
Norman Pavelka
author_facet Fabien Cottier
Alrina Shin Min Tan
Marina Yurieva
Webber Liao
Josephine Lum
Michael Poidinger
Francesca Zolezzi
Norman Pavelka
author_sort Fabien Cottier
collection DOAJ
description Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal (GI) microbiota were shown to keep C. albicans colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displays a synergistic effect in vitro with the absence of glucose in medium of culture, which underlines the complex interactions that C. albicans faces in its natural environment. Inactivation of the transcriptional regulator MIG1 in C. albicans results in a lack of sensitivity to this synergistic outcome. To decipher C. albicans transcriptional responses to glucose, WOAs, and the role of MIG1, we performed RNA sequencing (RNA-seq) on four biological replicates exposed to combinations of these three parameters. We were able to characterize the (i) glucose response, (ii) response to acetic and butyric acid, (iii) MIG1 regulation of C. albicans, and (iv) genes responsible for WOA resistance. We identified a group of six genes linked to WOA sensitivity in a glucose-MIG1-dependent manner and inactivated one of these genes, the putative glucose transporter HGT16, in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOA resistance in the absence of glucose. This result points toward a mechanism of WOA sensitivity in C. albicans involving membrane transporters, which could be exploited to control yeast colonization in human body niches.
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spelling doaj.art-e47667bb6a994f699a7cc6bf050161fe2022-12-21T22:55:38ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362017-11-017113597360410.1534/g3.117.3002384The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic AcidFabien CottierAlrina Shin Min TanMarina YurievaWebber LiaoJosephine LumMichael PoidingerFrancesca ZolezziNorman PavelkaCandida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal (GI) microbiota were shown to keep C. albicans colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displays a synergistic effect in vitro with the absence of glucose in medium of culture, which underlines the complex interactions that C. albicans faces in its natural environment. Inactivation of the transcriptional regulator MIG1 in C. albicans results in a lack of sensitivity to this synergistic outcome. To decipher C. albicans transcriptional responses to glucose, WOAs, and the role of MIG1, we performed RNA sequencing (RNA-seq) on four biological replicates exposed to combinations of these three parameters. We were able to characterize the (i) glucose response, (ii) response to acetic and butyric acid, (iii) MIG1 regulation of C. albicans, and (iv) genes responsible for WOA resistance. We identified a group of six genes linked to WOA sensitivity in a glucose-MIG1-dependent manner and inactivated one of these genes, the putative glucose transporter HGT16, in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOA resistance in the absence of glucose. This result points toward a mechanism of WOA sensitivity in C. albicans involving membrane transporters, which could be exploited to control yeast colonization in human body niches.http://g3journal.org/lookup/doi/10.1534/g3.117.300238short-chain fatty acidtranscriptomicsgene expression profilingRNA-seqglucose repressionMIG1Candida albicans
spellingShingle Fabien Cottier
Alrina Shin Min Tan
Marina Yurieva
Webber Liao
Josephine Lum
Michael Poidinger
Francesca Zolezzi
Norman Pavelka
The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid
G3: Genes, Genomes, Genetics
short-chain fatty acid
transcriptomics
gene expression profiling
RNA-seq
glucose repression
MIG1
Candida albicans
title The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid
title_full The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid
title_fullStr The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid
title_full_unstemmed The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid
title_short The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source, and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid
title_sort transcriptional response of candida albicans to weak organic acids carbon source and mig1 inactivation unveils a role for hgt16 in mediating the fungistatic effect of acetic acid
topic short-chain fatty acid
transcriptomics
gene expression profiling
RNA-seq
glucose repression
MIG1
Candida albicans
url http://g3journal.org/lookup/doi/10.1534/g3.117.300238
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