INVESTIGATION OF THE PERMEASE-FERROXIDASE PARTNERSHIP IN HIGH-AFFINITY IRON TRANSPORTERS IN CANDIDA ALBICANS

Abstract

The mammals employ sophisticated iron-sequestering systems to defend against microbial pathogens. The human fungal pathogen Candida albicans uses high-affinity iron transporters to acquire iron for survival and causing infection. A high-affinity iron transporter has two components: a ferroxidase and an iron permease. C. albicans possesses four permeases and five ferroxidases, indicating the presence of multiple iron transporters. In this thesis, I describe experiments and results that address the following objectives: (1) establish the partnerships between the multiple ferroxidases and permeases, (2) determine how the ferroxidases, permeases, and their partnerships are regulated, (3) elucidate the significance of different iron transporters for C. albicans to survive in various host niches with varied iron availability, and (4) define how each transporter contributes to host infection. The results shed new lights on how C. albicans obtains iron in the host and reveal novel therapeutic targets for treating this major infectious disease in humans.