Deletion of the copper transporter Ca CCC2 reveals two distinct pathways for iron acquisition in Candida albicans

Weissman, Ziva; Shemer, Revital; Kornitzer, Daniel

doi:10.1046/j.1365-2958.2002.02976.x

Cited by 89Fungal and yeast genetics researchFungal Infections and StudiesAntifungal resistance and susceptibility

Deletion of the copper transporter Ca CCC2 reveals two distinct pathways for iron acquisition in Candida albicans

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Weissman, Ziva, Shemer, Revital, Kornitzer, Daniel·2002·Molecular Microbiology

DOI 10.1046/j.1365-2958.2002.02976.x

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Abstract

Summary: Efficient iron acquisition is an essential requirement for growth of pathogenic organisms in the iron‐poor host environment. In Saccharomyces cerevisiae, high‐affinity iron import depends on the multicopper ferroxidase ScFet3. ScFet3 biogenesis in the trans‐Golgi compartment requires a copper‐transporting P‐type ATPase, ScCcc2. Here, we describe the isolation by functional complementation of a Ccc2 homologue from the pathogenic yeast Candida albicans. CaCcc2 is functionally distinct from a previously described C. albicans copper‐transporting P‐type ATPase, CaCrp1, which appears to be specifically involved in copper detoxification. Regulation of Ca CCC2 and the phenotype of the homozygous Ca CCC2 deletion indicate that it is required for high‐affinity iron import, making it the bona fide CCC2 homologue of C. albicans. Remarkably, in a mouse model of systemic infection, the Ca ccc2Δ strain displayed robust proliferation and no significant reduction in pathogenicity, suggesting the existence of alternative mechanisms of iron uptake from host tissues. We identify haemin and haemoglobin as potential iron sources that can be used by C. albicans in a CaCcc2‐independent manner.

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The oxidation of iron by multicopper oxidases requires copper, and this is supplied by the intracellular copper transporter Ccc2.
“The oxidation of iron by multicopper oxidases requires copper, and this is supplied by the intracellular copper transporter Ccc2 (Weissman et al., 2002).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Weissman et al., 2002
Adding heme or hemoglobin to iron-limited media improves the growth of Cryptococcus neoformans, Candida albicans, and Histoplasma capsulatum.
“The growth of C. neoformans, C. albicans, and H. capsulatum in iron-deplete media is enhanced upon addition of heme or hemoglobin (Foster, 2002; Hu et al., 2013; Weissman et al., 2002).”
From Iron in infection and immunity (2013) · cites this paper as Weissman et al., 2002

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Authors: Weissman, Z., Shemer, R., & Kornitzer, D.
Affiliations: Technion – Israel Institute of Technology (IL)
Corresponding author: Kornitzer, Daniel
ORCID: Shemer, Revital
Kornitzer, Daniel
Venue: Molecular Microbiology
Publisher: Wiley
Published: 2002-06
Volume: 44
Issue: 6
Pages: 1551-1560
ISSN: 0950-382X (ISSN-L)
1365-2958
DOI: 10.1046/j.1365-2958.2002.02976.x
OpenAlex: W1550150722
Cited by: 88
References: 50
Citations by year: 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 1 · 2014: 5 · 2013: 4 · 2012: 2
FWCI: 1.97
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 17 d)
Locations: Molecular Microbiology (publishedVersion)
PubMed (publishedVersion)
Funders: Ministry of Health, State of Israel
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords: Candida albicans, copper-transporting ATPase, iron acquisition, copper detoxification, hemin, hemoglobin, systemic infection, fungal pathogenicity
MeSH terms: Copper Transport Proteins, Adenosine Triphosphatases, Animals, Candida albicans, Copper, Disease Models, Animal, Genetic Complementation Test, Iron, Mice, Inbred BALB C, Molecular Sequence Data, Phenotype, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Gene Deletion, Membrane Transport Proteins, Cation Transport Proteins, Saccharomyces cerevisiae Proteins, Mice

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Deletion of the copper transporter Ca CCC2 reveals two distinct pathways for iron acquisition in Candida albicans

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