Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator

ABSTRACT Evolution of transcriptional control is essential for organisms to cope with diversification into a spectrum of environments, including environments with limited nutrients. Lysine biosynthesis in fungi occurs in eight enzymatic steps. In Saccharomyces cerevisiae, amino acid starvation elici...

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Autores principales:	Yumnam Priyadarshini, Krishnamurthy Natarajan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Candida albicans lysine biosynthesis transcriptional regulation transcriptional activator Gcn4 Lys14 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/72977fbc0971403385041611c1c45108
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spelling	oai:doaj.org-article:72977fbc0971403385041611c1c451082021-11-15T15:21:37ZReconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator10.1128/mSphere.00016-152379-5042https://doaj.org/article/72977fbc0971403385041611c1c451082016-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00016-15https://doaj.org/toc/2379-5042ABSTRACT Evolution of transcriptional control is essential for organisms to cope with diversification into a spectrum of environments, including environments with limited nutrients. Lysine biosynthesis in fungi occurs in eight enzymatic steps. In Saccharomyces cerevisiae, amino acid starvation elicits the induction of LYS gene expression, mediated by the master regulator Gcn4 and the pathway-specific transcriptional regulator Lys14. Here, we have shown that the activation of LYS gene expression in the human fungal pathogen Candida albicans is predominantly controlled by Gcn4 under amino acid starvation conditions. Multiple lines of study showed that the four C. albicansLYS14-like genes have no role in the regulation of lysine biosynthesis. Whereas Gcn4 is dispensable for the growth of S. cerevisiae under lysine deprivation conditions, it is an essential regulator required for the growth of C. albicans under these conditions, as gcn4 deletion caused lysine auxotrophy. Gcn4 is required for the induction of increased LYS2 and LYS9 mRNA but not for the induction of increased LYS4 mRNA. Under lysine or isoleucine-valine deprivation conditions, Gcn4 recruitment to LYS2 and LYS9 promoters was induced in C. albicans. Indeed, in contrast to the S. cerevisiaeLYS gene promoters, all LYS gene promoters in C. albicans harbored a Gcn4 binding site but not all harbored the S. cerevisiae Lys14 binding site, indicating the evolutionary divergence of cis-regulatory motifs. Thus, the transcriptional rewiring of the lysine biosynthetic pathway in C. albicans involves not only neofunctionalization of the four LYS14-like genes but the attendant strengthening of control by Gcn4, indicating a coordinated response with a much broader scope for control of amino acid biosynthesis in this human pathogen. IMPORTANCE Microbes evolve rapidly so as to reconfigure their gene expression to adapt to the metabolic demands in diverse environmental niches. Here, we explored how conditions of nutrient deprivation regulate lysine biosynthesis in the human fungal pathogen Candida albicans. We show that although both Saccharomyces cerevisiae and C. albicans respond to lysine deprivation by transcriptional upregulation of lysine biosynthesis, the regulatory factors required for this control have been reconfigured in these species. We found that Gcn4 is an essential and direct transcriptional regulator of the expression of lysine biosynthetic genes under lysine starvation conditions in C. albicans. Our results therefore suggest that the regulation of the lysine biosynthetic pathway in Candida clade genomes involves gain of function by the master transcriptional regulator Gcn4, coincident with the neofunctionalization of the S. cerevisiae pathway-specific regulator Lys14.Yumnam PriyadarshiniKrishnamurthy NatarajanAmerican Society for MicrobiologyarticleCandida albicanslysine biosynthesistranscriptional regulationtranscriptional activatorGcn4Lys14MicrobiologyQR1-502ENmSphere, Vol 1, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans lysine biosynthesis transcriptional regulation transcriptional activator Gcn4 Lys14 Microbiology QR1-502
spellingShingle	Candida albicans lysine biosynthesis transcriptional regulation transcriptional activator Gcn4 Lys14 Microbiology QR1-502 Yumnam Priyadarshini Krishnamurthy Natarajan Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator
description	ABSTRACT Evolution of transcriptional control is essential for organisms to cope with diversification into a spectrum of environments, including environments with limited nutrients. Lysine biosynthesis in fungi occurs in eight enzymatic steps. In Saccharomyces cerevisiae, amino acid starvation elicits the induction of LYS gene expression, mediated by the master regulator Gcn4 and the pathway-specific transcriptional regulator Lys14. Here, we have shown that the activation of LYS gene expression in the human fungal pathogen Candida albicans is predominantly controlled by Gcn4 under amino acid starvation conditions. Multiple lines of study showed that the four C. albicansLYS14-like genes have no role in the regulation of lysine biosynthesis. Whereas Gcn4 is dispensable for the growth of S. cerevisiae under lysine deprivation conditions, it is an essential regulator required for the growth of C. albicans under these conditions, as gcn4 deletion caused lysine auxotrophy. Gcn4 is required for the induction of increased LYS2 and LYS9 mRNA but not for the induction of increased LYS4 mRNA. Under lysine or isoleucine-valine deprivation conditions, Gcn4 recruitment to LYS2 and LYS9 promoters was induced in C. albicans. Indeed, in contrast to the S. cerevisiaeLYS gene promoters, all LYS gene promoters in C. albicans harbored a Gcn4 binding site but not all harbored the S. cerevisiae Lys14 binding site, indicating the evolutionary divergence of cis-regulatory motifs. Thus, the transcriptional rewiring of the lysine biosynthetic pathway in C. albicans involves not only neofunctionalization of the four LYS14-like genes but the attendant strengthening of control by Gcn4, indicating a coordinated response with a much broader scope for control of amino acid biosynthesis in this human pathogen. IMPORTANCE Microbes evolve rapidly so as to reconfigure their gene expression to adapt to the metabolic demands in diverse environmental niches. Here, we explored how conditions of nutrient deprivation regulate lysine biosynthesis in the human fungal pathogen Candida albicans. We show that although both Saccharomyces cerevisiae and C. albicans respond to lysine deprivation by transcriptional upregulation of lysine biosynthesis, the regulatory factors required for this control have been reconfigured in these species. We found that Gcn4 is an essential and direct transcriptional regulator of the expression of lysine biosynthetic genes under lysine starvation conditions in C. albicans. Our results therefore suggest that the regulation of the lysine biosynthetic pathway in Candida clade genomes involves gain of function by the master transcriptional regulator Gcn4, coincident with the neofunctionalization of the S. cerevisiae pathway-specific regulator Lys14.
format	article
author	Yumnam Priyadarshini Krishnamurthy Natarajan
author_facet	Yumnam Priyadarshini Krishnamurthy Natarajan
author_sort	Yumnam Priyadarshini
title	Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator
title_short	Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator
title_full	Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator
title_fullStr	Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator
title_full_unstemmed	Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator
title_sort	reconfiguration of transcriptional control of lysine biosynthesis in <named-content content-type="genus-species">candida albicans</named-content> involves a central role for the gcn4 transcriptional activator
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/72977fbc0971403385041611c1c45108
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Reconfiguration of Transcriptional Control of Lysine Biosynthesis in <named-content content-type="genus-species">Candida albicans</named-content> Involves a Central Role for the Gcn4 Transcriptional Activator

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