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Candida albicans Hap43 Is a Repressor Induced under Low-Iron Conditions and Is Essential for Iron-Responsive Transcriptional Regulation and Virulence
Open accessAbstract
Candida albicans is an opportunistic fungal pathogen that exists as normal flora in healthy human bodies but causes life-threatening infections in immunocompromised patients. In addition to innate and adaptive immunities, hosts also resist microbial infections by developing a mechanism of “natural resistance” that maintains a low level of free iron to restrict the growth of invading pathogens. C. albicans must overcome this iron-deprived environment to cause infections. There are three types of iron-responsive transcriptional regulators in fungi; Aft1/Aft2 activators in yeast, GATA-type repressors in many fungi, and HapX/Php4 in Schizosaccharomyces pombe and Aspergillus species. In this study, we characterized the iron-responsive regulator Hap43, which is the C. albicans homolog of HapX/Php4 and is repressed by the GATA-type repressor Sfu1 under iron-sufficient conditions. We provide evidence that Hap43 is essential for the growth of C. albicans under low-iron conditions and for C. albicans virulence in a mouse model of infection. Hap43 was not required for iron acquisition under low-iron conditions. Instead, it was responsible for repression of genes that encode iron-dependent proteins involved in mitochondrial respiration and iron-sulfur cluster assembly. We also demonstrated that Hap43 executes its function by becoming a transcriptional repressor and accumulating in the nucleus in response to iron deprivation. Finally, we found a connection between Hap43 and the global corepressor Tup1 in low-iron-induced flavinogenesis. Taken together, our data suggest a complex interplay among Hap43, Sfu1, and Tup1 to coordinately regulate iron acquisition, iron utilization, and other iron-responsive metabolic activities.
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“Finally, it has been recently reported that Hap43, Sfu1, and Tup1 act coordinately and regulate iron acquisition, iron utilization, and other iron-responsive metabolic activities in C. albicans [75].”
From Strategies of intracellular pathogens for obtaining iron from the environment (2015) · cites this paper as [75]
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Clustal W and Clustal X version 2.0
Larkin, M., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., López, R., et al. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm404 · Cited by 28,598
Oxygen toxicity, oxygen radicals, transition metals and disease
Halliwell, B., & Gutteridge, J. M. C. (1984) · Biochemical Journal · doi:10.1042/bj2190001 · Cited by 5,330
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736
Isogenic strain construction and gene mapping in Candida albicans.
Fonzi, W. A., & Irwin, M. Y. (1993) · Genetics · doi:10.1093/genetics/134.3.717 · Cited by 1,695
Gillum, A. M., Tsay, E. Y. H., & Kirsch, D. R. (1984) · Molecular and General Genetics MGG · doi:10.1007/bf00328721 · Cited by 1,253
Secretion of Flavins by Shewanella Species and Their Role in Extracellular Electron Transfer
von Canstein, H., Ogawa, J., Shimizu, S., & Lloyd, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.01387-07 · Cited by 912
Biologically relevant metal ion‐dependent hydroxyl radical generation An update
Halliwell, B. B., & Gutteridge, J. M. C. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)80911-y · Cited by 884
MatGAT: An application that generates similarity/identity matrices using protein or DNA sequences
Campanella, J. J., Bitincka, L., & Smalley, J. V. (2003) · BMC Bioinformatics · doi:10.1186/1471-2105-4-29 · Cited by 857
The SAT1 flipper, an optimized tool for gene disruption in Candida albicans
Reuß, O., Vik, Å., Kolter, R., & Morschhäuser, J. (2004) · Gene · doi:10.1016/j.gene.2004.06.021 · Cited by 744
Lack of a role for iron in the Lyme disease pathogen
Posey, J. E., & Gherardini, F. C. (2000) · Science · doi:10.1126/science.288.5471.1651 · Cited by 538
Research works printed but not linked: 1
- SambrookJ. RussellD. W. . 2001. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
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Finkel, J. S., Xu, W., Huang, D., Hill, E. M., Desai, J. V., Woolford, C. A., Nett, J. E., Taff, H., Norice, C. T., Andes, D. R., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002525 · Cited by 228
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Metadata
- Authors
- Hsu, P.-C., Yang, C.-Y., & Lan, C.-Y.
- Affiliations
- Institute of Molecular and Cellular Biology, No. 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan, Republic of China
- Animal Technology Institute Taiwan (TW)
- National Tsing Hua University (TW)
- Corresponding author
- Lan, Chung-Yu
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2011-02
- Volume
- 10
- Issue
- 2
- Pages
- 207-225
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC3067405
- OpenAlex
- W2146920262
- Cited by
- 157
- References
- 94
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 8 · 2014: 13 · 2013: 14 · 2012: 14
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Keywords
- Candida albicans, iron starvation, Tup1, iron acquisition, iron-sulfur cluster assembly, mitochondrial respiration, fungal virulence, natural resistance to infection, transcriptional repressor
- MeSH terms
- Iron Deficiencies, Amino Acid Sequence, Animals, Candida albicans, Candidiasis, Cell Nucleus, Female, Flavins, Fungal Proteins, Humans, Iron, Kidney, Mice, Inbred BALB C, Molecular Sequence Data, Repressor Proteins, Virulence, Gene Expression Regulation, Fungal, Sequence Alignment, Gene Deletion, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Cell Proliferation, Mice
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