title: Adaptation of Cryptococcus neoformans to mammalian hosts: integrated regulation of metabolism and virulence.
abstract: The basidiomycete fungus Cryptococcus neoformans infects humans via inhalation of desiccated yeast cells or spores from the environment. In the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. The fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream, and central nervous system. Recent studies provide insights into mechanisms of adaptation during this transition that include the expression of antiphagocytic functions, the remodeling of central carbon metabolism, the expression of specific nutrient acquisition systems, and the response to hypoxia. Specific transcription factors regulate these functions as well as the expression of one or more of the major known virulence factors of C. neoformans. Therefore, virulence factor expression is to a large extent embedded in the regulation of a variety of functions needed for growth in mammalian hosts. In this regard, the complex integration of these processes is reminiscent of the master regulators of virulence in bacterial pathogens.
authors.affiliation: The Michael Smith Laboratories, Department of Microbiology and Immunology, and Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC, Canada. kronstad@msl.ubc.ca
authors.forename: Jim
authors.initials: J
authors.lastname: Kronstad
authors.forename: Sanjay
authors.initials: S
authors.lastname: Saikia
authors.forename: Erik David
authors.initials: ED
authors.lastname: Nielson
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretschmer
authors.forename: Wonhee
authors.initials: W
authors.lastname: Jung
authors.forename: Guanggan
authors.initials: G
authors.lastname: Hu
authors.forename: Jennifer M H
authors.initials: JM
authors.lastname: Geddes
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Griffiths
authors.forename: Jaehyuk
authors.initials: J
authors.lastname: Choi
authors.forename: Brigitte
authors.initials: B
authors.lastname: Cadieux
authors.forename: Mélissa
authors.initials: M
authors.lastname: Caza
authors.forename: Rodgoun
authors.initials: R
authors.lastname: Attarian
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D003455:Cryptococcus neoformans / Q000472:pathogenicity* / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism; D008322:Mammals; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D037521:Virulence Factors; D007501:Iron