Iron acquisition in the human fungal pathogen Cryptococcus neoformans

• C. neoformans possesses high-affinity and low-affinity iron uptake systems.
• The reductive high-affinity iron uptake system is required for virulence.
• The regulation of iron uptake is mediated by a number of different regulatory proteins.
• Microenvironmental conditions in the host influence iron acquisition.

Iron sequestration by the vertebrate host is considered an efficient defense mechanism against pathogenic microbes. However, this mechanism, so called nutritional immunity, is often overcome by the iron acquisition systems that have evolved in microbial pathogens. Numerous studies have been carried out to identify the key components of these systems and to understand their underlying mechanisms, including recent investigations in the basidiomycete fungal pathogen Cryptococcus neoformans. Iron acquisition is essential for the survival and pathogenesis of this fungus within vertebrate hosts. Growing evidence suggests that the fungus is able to utilize several different iron sources available in the host, and that the intracellular or extracellular localization of the pathogen influences its iron acquisition strategy. Herein, we review current findings on the components and regulatory elements of the iron acquisition systems in C. neoformans.