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Published on: March 19, 2019
Utilization of ferroproteins by Candida albicans during candidastasis by apotransferrin
1College of Pharmacy, Dongduk Women's University, 23-1 Wolgok-dong, Sungbuk-gu, Seoul 136-714, Korea. ymhan@dongduk.ac.kr
Abstract:
Many reports have stated that some of the pathogenic bacteria can obtain iron from ferroproteins, such as cytochrome C, ferritin, hemin, hemoglobin, and myoglobin. These reports prompted us to determine if an opportunistic pathogenic fungus, Candida albicans, can utilize ferroproteins to circumvent the iron-regulatory effect of transferrin. The following assays were carried out to measure in vitro growth stimulation by the ferroproteins: as an initial step, C. albicans was cultured in iron-free (pretreated with apotransferrin for 24 h) culture medium. Once Candida albicans yeast cell growth reached stasis from iron starvation, individual ferroproteins were added to the culture media. Results showed that hemin, hemoglobin, and myoglobin supported a partial growth recovery. Additional studies with haptoglobin, a serum protein that interacts with the globin moiety of certain ferroproteins, established that C. albicans could obtain iron from the haptoglobin-ferroprotein complexes. These data indicate that the heme part of the ferroproteins is the source of iron. This implies that heme oxygenase, CaHMX1 might be involved in bringing about dissociation of heme-containing protein for iron-acquisition. In addition, anticandidal activity of transferrin takes place not only by the process of iron regulation, but also by direct interaction with the yeast cells.
Insights
Candida albicans can acquire iron from ferroproteins like hemoglobin, bypassing transferrin's iron regulation. This suggests heme oxygenase may be involved in iron acquisition by this opportunistic fungus.
Area of Science:
- Mycology
- Infectious Diseases
- Biochemistry
Background:
- Pathogenic bacteria utilize ferroproteins for iron acquisition.
- Transferrin regulates iron availability, impacting microbial growth.
- Candida albicans is an opportunistic fungal pathogen.
Purpose of the Study:
- To investigate if Candida albicans can utilize ferroproteins to overcome transferrin-mediated iron restriction.
- To identify specific ferroproteins that support C. albicans growth.
- To explore the mechanism of iron acquisition from ferroproteins by C. albicans.
Main Methods:
- In vitro culture of C. albicans under iron-limiting conditions.
- Addition of various ferroproteins (hemin, hemoglobin, myoglobin, haptoglobin complexes) to assess growth recovery.
- Analysis of iron source from ferroproteins.
Main Results:
- Hemin, hemoglobin, and myoglobin partially restored C. albicans growth.
- C. albicans could utilize iron from haptoglobin-ferroprotein complexes.
- The heme moiety of ferroproteins is the primary source of iron.
- Transferrin exhibits direct anticandidal activity beyond iron regulation.
Conclusions:
- Candida albicans can acquire iron from specific ferroproteins, circumventing transferrin's inhibitory effects.
- The heme group is crucial for iron acquisition from these proteins.
- Heme oxygenase (CaHMX1) may play a role in iron release from heme-containing proteins.
- Transferrin possesses dual anticandidal mechanisms: iron withholding and direct cell interaction.
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