Open AccessThe Mannoprotein Cig1 Supports Iron Acquisition From Heme and Virulence in the Pathogenic Fungus Cryptococcus neoformans
Author(s) -
Brigitte Cadieux,
Tianshun Lian,
Guanggan Hu,
Joyce Wang,
Carmelo Biondo,
Giuseppe Teti,
Victor Liu,
M.E.P. Murphy,
A. Louise Creagh,
James W. Kronstad
Publication year - 2013
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1093/infdis/jit029
Subject(s) - cryptococcus neoformans , heme , virulence , microbiology and biotechnology , virulence factor , mutant , biology , fungal protein , extracellular , biochemistry , fungus , gene , enzyme , botany
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.