title: Metabolism in fungal pathogenesis.
abstract: Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host-fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies.
authors.affiliation: Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Iuliana V
authors.initials: IV
authors.lastname: Ene
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, 07745 Jena, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Brunke
authors.affiliation: Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Hans Knoell Institute, 07745 Jena, Germany Friedrich Schiller University, 07743 Jena, Germany Center for Sepsis Control and Care, Universitätsklinikum Jena, 07747 Jena, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
mesh_terms: D002177:Candidiasis / Q000209:etiology / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D005658:Fungi / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism; D018977:Micronutrients / Q000378:metabolism; D009181:Mycoses / Q000209:etiology / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D018977:Micronutrients; D037521:Virulence Factors; D002244:Carbon; D007501:Iron; D015032:Zinc; D009584:Nitrogen