A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts

ABSTRACT Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast Candida glabrata have thus developed effective iron acquisition strategies. Their reg...

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Autores principales: Franziska Gerwien, Abu Safyan, Stephanie Wisgott, Fabrice Hille, Philipp Kaemmer, Jörg Linde, Sascha Brunke, Lydia Kasper, Bernhard Hube
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Publicado: American Society for Microbiology 2016
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spelling oai:doaj.org-article:8faf2cbb43c74ec3af99f3e71d433ee42021-11-15T15:50:15ZA Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts10.1128/mBio.01782-162150-7511https://doaj.org/article/8faf2cbb43c74ec3af99f3e71d433ee42016-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01782-16https://doaj.org/toc/2150-7511ABSTRACT Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast Candida glabrata have thus developed effective iron acquisition strategies. Their regulation has been investigated well for some pathogenic fungi and in the model organism Saccharomyces cerevisiae, which employs an evolutionarily derived system. Here, we show that C. glabrata uses a regulation network largely consisting of components of the S. cerevisiae regulon but also of elements of other pathogenic fungi. Specifically, similarly to baker’s yeast, Aft1 is the main positive regulator under iron starvation conditions, while Cth2 degrades mRNAs encoding iron-requiring enzymes. However, unlike the case with S. cerevisiae, a Sef1 ortholog is required for full growth under iron limitation conditions, making C. glabrata an evolutionary intermediate to SEF1-dependent fungal pathogens. Therefore, C. glabrata has evolved an iron homeostasis system which seems to be unique within the pathogenic fungi. IMPORTANCE The fungus Candida glabrata represents an evolutionarily close relative of the well-studied and benign baker’s yeast and model organism Saccharomyces cerevisiae. On the other hand, C. glabrata is an important opportunistic human pathogen causing both superficial and systemic infections. The ability to acquire trace metals, in particular, iron, and to tightly regulate this process during infection is considered an important virulence attribute of a variety of pathogens. Importantly, S. cerevisiae uses a highly derivative regulatory system distinct from those of other fungi. Until now, the regulatory mechanism of iron homeostasis in C. glabrata has been mostly unknown. Our study revealed a hybrid iron regulation network that is unique to C. glabrata and is placed at an evolutionary midpoint between those of S. cerevisiae and related fungal pathogens. We thereby show that, in the host, even a successful human pathogen can rely largely on a strategy normally found in nonpathogenic fungi from a terrestrial environment.Franziska GerwienAbu SafyanStephanie WisgottFabrice HillePhilipp KaemmerJörg LindeSascha BrunkeLydia KasperBernhard HubeAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 5 (2016)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Franziska Gerwien
Abu Safyan
Stephanie Wisgott
Fabrice Hille
Philipp Kaemmer
Jörg Linde
Sascha Brunke
Lydia Kasper
Bernhard Hube
A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts
description ABSTRACT Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast Candida glabrata have thus developed effective iron acquisition strategies. Their regulation has been investigated well for some pathogenic fungi and in the model organism Saccharomyces cerevisiae, which employs an evolutionarily derived system. Here, we show that C. glabrata uses a regulation network largely consisting of components of the S. cerevisiae regulon but also of elements of other pathogenic fungi. Specifically, similarly to baker’s yeast, Aft1 is the main positive regulator under iron starvation conditions, while Cth2 degrades mRNAs encoding iron-requiring enzymes. However, unlike the case with S. cerevisiae, a Sef1 ortholog is required for full growth under iron limitation conditions, making C. glabrata an evolutionary intermediate to SEF1-dependent fungal pathogens. Therefore, C. glabrata has evolved an iron homeostasis system which seems to be unique within the pathogenic fungi. IMPORTANCE The fungus Candida glabrata represents an evolutionarily close relative of the well-studied and benign baker’s yeast and model organism Saccharomyces cerevisiae. On the other hand, C. glabrata is an important opportunistic human pathogen causing both superficial and systemic infections. The ability to acquire trace metals, in particular, iron, and to tightly regulate this process during infection is considered an important virulence attribute of a variety of pathogens. Importantly, S. cerevisiae uses a highly derivative regulatory system distinct from those of other fungi. Until now, the regulatory mechanism of iron homeostasis in C. glabrata has been mostly unknown. Our study revealed a hybrid iron regulation network that is unique to C. glabrata and is placed at an evolutionary midpoint between those of S. cerevisiae and related fungal pathogens. We thereby show that, in the host, even a successful human pathogen can rely largely on a strategy normally found in nonpathogenic fungi from a terrestrial environment.
format article
author Franziska Gerwien
Abu Safyan
Stephanie Wisgott
Fabrice Hille
Philipp Kaemmer
Jörg Linde
Sascha Brunke
Lydia Kasper
Bernhard Hube
author_facet Franziska Gerwien
Abu Safyan
Stephanie Wisgott
Fabrice Hille
Philipp Kaemmer
Jörg Linde
Sascha Brunke
Lydia Kasper
Bernhard Hube
author_sort Franziska Gerwien
title A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts
title_short A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts
title_full A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts
title_fullStr A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts
title_full_unstemmed A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts
title_sort novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts
publisher American Society for Microbiology
publishDate 2016
url https://doaj.org/article/8faf2cbb43c74ec3af99f3e71d433ee4
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