The Hyphal Associated Adhesin and Invasin Als3 of Candida albicans Mediates Iron Acquisition from Host Ferritin. Candida albicans

Iron sequestration by host iron-binding proteins is an important mechanism of resistance to microbial infections. Inside oral epithelial cells, iron is stored within the ferritin, and is therefore usually not accessible to pathogenic microbes. We observed that the ferritin concentration within oral epithelial cells was directly related to their susceptibility to damage by the human pathogenic fungus Candida albicans. Thus, we hypothesized that host ferritin may be used as an iron source by this organism. A screen of C. albicans mutants lacking components of each of the three iron acquisition systems revealed that only the reductive pathway is involved in iron utilization from ferritin by this organism. Transcriptional profiling of wild-type and hyphal-defective C. albicans strains suggested that the C. albicans invasin-like protein Als3 plays a role in ferritin binding. Overall design: Total RNA from wild-type (CAI4) and hyphal-defective C. albicans strains (deltaHGC1, deltaRAS1) was prepared after growth under iron-limiting conditions. Each strain was labeled and compared to a common control (C. albicans strain SC5314) in four independent experiments including two dye swaps.