title: Histidine degradation via an aminotransferase increases the nutritional flexibility of Candida glabrata.
abstract: The ability to acquire nutrients during infections is an important attribute in microbial pathogenesis. Amino acids are a valuable source of nitrogen if they can be degraded by the infecting organism. In this work, we analyzed histidine utilization in the fungal pathogen of humans Candida glabrata. Hemiascomycete fungi, like C. glabrata or Saccharomyces cerevisiae, possess no gene coding for a histidine ammonia-lyase, which catalyzes the first step of a major histidine degradation pathway in most other organisms. We show that C. glabrata instead initializes histidine degradation via the aromatic amino acid aminotransferase Aro8. Although ARO8 is also present in S. cerevisiae and is induced by extracellular histidine, the yeast cannot use histidine as its sole nitrogen source, possibly due to growth inhibition by a downstream degradation product. Furthermore, C. glabrata relies only on Aro8 for phenylalanine and tryptophan utilization, since ARO8, but not its homologue ARO9, was transcriptionally activated in the presence of these amino acids. Accordingly, an ARO9 deletion had no effect on growth with aromatic amino acids. In contrast, in S. cerevisiae, ARO9 is strongly induced by tryptophan and is known to support growth on aromatic amino acids. Differences in the genomic structure of the ARO9 gene between C. glabrata and S. cerevisiae indicate a possible disruption in the regulatory upstream region. Thus, we show that, in contrast to S. cerevisiae, C. glabrata has adapted to use histidine as a sole source of nitrogen and that the aromatic amino acid aminotransferase Aro8, but not Aro9, is the enzyme required for this process.
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany sascha.brunke@hki-jena.de bernhard.hube@hki-jena.de.
authors.forename: Sascha
authors.initials: S
authors.lastname: Brunke
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Seider
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany Institute for Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany.
authors.forename: Martin Ernst
authors.initials: ME
authors.lastname: Richter
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Bremer-Streck
authors.affiliation: Research Group Microbial Biochemistry and Physiology, Hans Knoell Institute, Jena, Germany.
authors.forename: Shruthi
authors.initials: S
authors.lastname: Ramachandra
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany Institute for Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehntopf
authors.affiliation: Research Group Microbial Biochemistry and Physiology, Hans Knoell Institute, Jena, Germany Friedrich Schiller University, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brock
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, Jena, Germany Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany Friedrich Schiller University, Jena, Germany sascha.brunke@hki-jena.de bernhard.hube@hki-jena.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
mesh_terms: D041221:Candida glabrata / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D013045:Species Specificity; D013379:Substrate Specificity; D000637:Transaminases / Q000235:genetics / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D010649:Phenylalanine; D006639:Histidine; D014364:Tryptophan; D000637:Transaminases; C019729:aromatic amino acid aminotransferase; D009584:Nitrogen
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