Figure 2.

Multiple characterized and uncharacterized iron acquisition systems may contribute to the virulence of C. neoformans. A hypothetical virulence assay is depicted in which 100% of the mice infected with a wild-type strain succumb to cryptococcosis in a relatively short period of time. Mutants defective in high affinity iron uptake functions (designated high affinity) such as Cft1 or CfO1 have reduced virulence resulting in longer survival of infected mice [23, 24]. A mutant lacking both the high affinity system and the ability to take up heme (e.g., a cfO1 cig1 mutant designated high affinity, heme) is further attenuated for virulence [26]. It is possible that the addition of further mutations to block reductase activity (reductases?) will also partially attenuate virulence. Finally, defects in characterized and uncharacterized (low affinity?) systems, and mutations in yet to be discovered iron uptake functions (other mechanisms?) may be required to completely eliminate disease. The time for a complete assay in the mouse inhalation model of cryptococcosis (as shown) is typically ∼60 days. The survival patterns associated with the wild-type strain or mutants with defects in characterized iron acquisition systems are indicated with solid lines while the hypothesized patterns for mutants lacking combinations of characterized and uncharacterized systems are shown with dashed lines.