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Updated: Mar 15, 2026

The Caco-2 Cell Bioassay for Measurement of Food Iron Bioavailability
Published on: April 28, 2022
Differentially regulated high-affinity iron assimilation systems support growth of the various cell types in the
Shivani Pasricha1, Lukas Schafferer2, Herbert Lindner2
1Department of Genetics, University of Melbourne, Victoria, 3010, Australia.
Abstract:
Iron is a key trace element important for many biochemical processes and its availability varies with the environment. For human pathogenic fungi iron acquisition can be particularly problematical because host cells sequester free iron as part of the acute-phase response to infection. Fungi rely on high-affinity iron uptake systems, such as reductive iron assimilation (RIA) and siderophore-mediated iron uptake (non-RIA). These have been extensively studied in pathogenic fungi that exist outside of host cells, but much less is known for intracellular fungal pathogens. Talaromyces marneffei is a dimorphic fungal pathogen endemic to Southeast Asia. In the host T. marneffei resides within macrophages where it grows as a fission yeast. T. marneffei has genes of both iron assimilation systems as well as a paralogue of the siderophore biosynthetic gene sidA, designated sidX. Unlike other fungi, deletion of sidA or sidX resulted in cell type-specific effects. Mutant analysis showed that T. marneffei yeast cells also employ RIA for iron acquisition, providing an additional system in this cell type that differs substantially from hyphal cells. These data illustrate the specialized iron acquisition systems used by the different cell types of a dimorphic fungal pathogen and highlight the complexity in siderophore-biosynthetic pathways amongst fungi.
Insights
Human pathogenic fungi like Talaromyces marneffei have specialized iron uptake systems. This study reveals distinct iron assimilation strategies in yeast versus hyphal forms, crucial for survival within host macrophages.
Area of Science:
- Medical Mycology
- Molecular Biology
- Biochemistry
Background:
- Iron is essential for fungal growth, but its availability is limited within host environments.
- Human pathogenic fungi utilize high-affinity iron uptake systems, including reductive iron assimilation (RIA) and siderophore-mediated uptake (non-RIA).
- Intracellular fungal pathogens face unique challenges in acquiring iron due to host immune responses.
Purpose of the Study:
- To investigate the iron acquisition mechanisms of Talaromyces marneffei, a dimorphic fungal pathogen.
- To understand how T. marneffei adapts its iron uptake strategies between its yeast and hyphal forms.
- To explore the roles of specific iron assimilation genes, including sidA and sidX, in T. marneffei.
Main Methods:
- Comparative analysis of iron assimilation genes in T. marneffei.
- Mutant analysis of sidA and sidX genes to assess their impact on iron uptake.
- Investigation of iron acquisition systems in both yeast and hyphal cell types of T. marneffei.
Main Results:
- Talaromyces marneffei possesses genes for both RIA and non-RIA iron uptake systems.
- Deletion of sidA or sidX genes exhibited cell type-specific effects on iron acquisition.
- T. marneffei yeast cells utilize RIA, an additional system distinct from hyphal cells, for iron acquisition.
Conclusions:
- Talaromyces marneffei employs specialized and distinct iron acquisition systems in its different cell types (yeast vs. hyphae).
- The complexity of siderophore biosynthesis pathways varies among fungal species.
- Understanding these specialized systems is crucial for developing targeted antifungal therapies against intracellular pathogens.
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