Mamouei, Z., Zeng, G., Wang, Y.‐M. and Wang, Y. (2017), Candida albicans possess a highly versatile and dynamic high‐affinity iron transport system important for its commensal‐pathogenic lifestyle. Molecular Microbiology, 106: 986-998. doi:10.1111/mmi.13864
Abstract:
Iron is an essential nutrient for nearly all organisms, but iron overdose is toxic. The human commensal‐pathogenic fungus Candida albicans traverses host niches with markedly different iron availability. During systemic infection, C. albicans must activate the high‐affinity iron permease Ftr1 to acquire iron sequestered by the host's iron‐withholding defense and suppresses iron uptake while residing in the iron‐rich gut to avoid toxicity. Ftr1 associates with a ferroxidase to form an iron transporter. C. albicans contains four permeases and five ferroxidase homologs, suggesting 20 possible subunit combinations. Here, we investigated the iron‐dependent expression, cellular localization and interacting partners of all permeases and ferroxidases and the significance of each subunit for gastrointestinal colonization and systemic infection in mice. We uncovered three distinct patterns of iron‐dependent expression and highly flexible ferroxidase‐permease partnerships, which underlie a dynamic iron transport system that can be deftly tuned according to iron availability. We found functional differentiation as well as redundancy among the ferroxidases and permeases during both gastrointestinal colonization and bloodstream infection. We propose that C. albicans possesses a sophisticated iron acquisition and utilization system befitting its commensal‐pathogenic lifestyle. Our findings reveal new possibilities for medical intervention of C. albicans infection.
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Funding Info:
This work was supported by the Core budget to IMCB.
Description:
This is the peer reviewed version of the following article: Mamouei, Z., Zeng, G., Wang, Y.‐M. and Wang, Y. (2017), Candida albicans possess a highly versatile and dynamic high‐affinity iron transport system important for its commensal‐pathogenic lifestyle. Molecular Microbiology, 106: 986-998. https://doi.org/10.1111/mmi.13864, which has been published in final form at https://doi.org/10.1111/mmi.13864. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.