The Mannoprotein Cig1 supports iron acquisition from heme and virulence in the pathogenic fungus Cryptococcus neoformans.

Iron acquisition is critical for virulence of the human pathogenic fungus Cryptococcus neoformans. The cryptococcal transcript for the extracellular mannoprotein Cig1 is highly regulated by iron and abundant in iron-starved cells, suggesting a role in iron acquisition. Indeed, loss of Cig1 resulted...

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Publicado en:Journal of Infectious Diseases Vol. 207; no. 8; pp. 1339 - 1348
Autores principales: Cadieux, Brigitte, Lian, Tianshun, Hu, Guanggan, Wang, Joyce, Biondo, Carmelo, Teti, Giuseppe, Liu, Victor, Murphy, Michael E P, Creagh, A Louise, Kronstad, James W
Formato: research Journal Article
Publicado: Oxford University Press / USA Apr2013
Acceso en línea:Ver este registro en EBSCOhost
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        atl: The Mannoprotein Cig1 supports iron acquisition from heme and virulence in the pathogenic fungus Cryptococcus neoformans.
      aug:
        au:
          Cadieux, Brigitte
          Lian, Tianshun
          Hu, Guanggan
          Wang, Joyce
          Biondo, Carmelo
          Teti, Giuseppe
          Liu, Victor
          Murphy, Michael E P
          Creagh, A Louise
          Kronstad, James W
        affil: Michael Smith Laboratories and Department of Microbiology and Immunology, The University of British Columbia, Vancouver, BC, Canada.
      sug:
        subj:
          Cryptococcosis Pathology
          Cryptococcus
          Iron Metabolism
          Metalloporphyrins Metabolism
          Proteins Metabolism
          Animal Studies
          Colony Count, Microbial
          Cryptococcosis Microbiology
          Female
          Genes
          Hydrogen-Ion Concentration
          Mice
          Proteins
          Recombinant Proteins
          Recombinant Proteins Metabolism
          RNA
          Spectrophotometry Methods
          Titrimetry
          Toxins
          Toxins Metabolism
          Female
      ab: Iron acquisition is critical for virulence of the human pathogenic fungus Cryptococcus neoformans. The cryptococcal transcript for the extracellular mannoprotein Cig1 is highly regulated by iron and abundant in iron-starved cells, suggesting a role in iron acquisition. Indeed, loss of Cig1 resulted in delayed growth on heme at physiological pH. Expression of CIG1 is regulated by the pH-responsive transcription factor Rim101, and loss of Rim101 also impaired growth on heme. A cig1Δ mutant was less susceptible than the wild-type strain to noniron metalloporphyrins, further indicating a role for Cig1 in heme uptake. Recombinant Cig1 exhibited the absorbance spectrum of a heme-binding protein upon heme titration, and Cig1 may therefore function as a hemophore at the cell surface. Cig1 contributed to virulence in a mouse model of cryptococcosis but only in a mutant that also lacked the high-affinity iron uptake system. Overall, Cig1-mediated heme uptake is a potential therapeutic target in C. neoformans.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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