title: 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 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.
  
  
  
  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.
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany.
authors: Franziska
authors: F
authors: Gerwien
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany.
authors: Abu
authors: A
authors: Safyan
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany.
authors: Stephanie
authors: S
authors: Wisgott
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany.
authors: Fabrice
authors: F
authors: Hille
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany.
authors: Philipp
authors: P
authors: Kaemmer
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Research Group Systems Biology and Bioinformatics, Jena, Germany.
authors: Jörg
authors: J
authors: Linde
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany.
authors: Sascha
authors: S
authors: Brunke
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany.
authors: Lydia
authors: L
authors: Kasper
authors: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Department of Microbial Pathogenicity Mechanisms, Jena, Germany Bernhard.Hube@leibniz-hki.de.|Friedrich Schiller University, Jena, Germany.|Center for Sepsis Control and Care (CSCC), University Hospital Jena, Jena, Germany.
authors: Bernhard
authors: B
authors: Hube
mesh_terms: D041221:Candida glabrata / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D019143:Evolution, Molecular; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D007501:Iron / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D007501:Iron