5 years ago

Candida albicans possess a highly versatile and dynamic high-affinity iron transport system important for its commensal-pathogenic lifestyle

Candida albicans possess a highly versatile and dynamic high-affinity iron transport system important for its commensal-pathogenic lifestyle
Yan-Ming Wang, Zeinab Mamouei, Yue Wang, Guisheng Zeng
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 permease 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. This article is protected by copyright. All rights reserved. All organisms must strike a delicate balance between acquiring the essential nutrient iron and avoiding its toxicity. We demonstrate that the human fungal pathogen Candida albicans has evolved a sophisticated, robust iron acquisition system that can assemble different sets of high-affinity iron transporters according to iron availability. This trait especially suits the commensal-pathogenic lifestyle of C. albicans that traverses host niches with drastically different levels of iron supply.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/mmi.13864

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