An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis

Chen, Changbin; Pande, Kalyan; French, Sarah D.; Tuch, Brian B.; Noble, Suzanne M.

doi:10.1016/j.chom.2011.07.005

Cited by 317Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis

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Chen, Changbin, Pande, Kalyan, French, Sarah D., Tuch, Brian B., Noble, Suzanne M.·2011·Cell Host & Microbe

DOI 10.1016/j.chom.2011.07.005PMC PMC3165008

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Abstract

The mammalian gastrointestinal tract and bloodstream are highly disparate biological niches that differ in concentrations of nutrients such as iron. However, some commensal-pathogenic microorganisms, such as the yeast Candida albicans, thrive in both environments. We report the evolution of a transcription circuit in C. albicans that controls iron uptake and determines its fitness in both niches. Our analysis of DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved iron-responsive transcriptional repressors, Sfu1 and Hap43. Sef1 activates iron-uptake genes and promotes virulence in a mouse model of bloodstream infection, whereas Sfu1 represses iron-uptake genes and is dispensable for virulence but promotes gastrointestinal commensalism. Thus, C. albicans can alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut, and this may represent a fundamental attribute of gastrointestinal commensal-pathogens.

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During systemic infection with occurrence of C. albicans in the bloodstream, low iron availability leads to the expression and nuclear localization of Sef1.
“During systemic infection with occurrence of C. albicans in the bloodstream, low iron availability leads to the expression and nuclear localization of Sef1 (Chen et al., 2011).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Chen et al., 2011
In Results, “SEF1 and SFU1 are differentially expressed in the bloodstream and gut” (page not specified), SEF1 expression is reported as twofold higher in human plasma than in the murine gut, and the authors describe the bloodstream as an iron-poor niche. The cited paper does not report that low iron causes Sef1 to localize to the nucleus during systemic infection; that part of the claim is unsupported. (LLM, conf=0.86)
Experimental — accuracy not yet measured
During iron-depleted conditions, Sef1 is induced and activated by Ssn3 and induces expression of HAP43 and iron acquisition genes.
“During iron depleted conditions, Sef1 is induced and activated by Ssn3 (Chen and Noble, 2012), and induces the expression of HAP43 and iron acquisition genes (Chen et al., 2011).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Chen et al., 2011
C. albicans has a tight iron regulation system including 3 major transcriptional regulators, Sef1p, Sfu1p, and the Hap43p-associated CCAAT-binding complex.
“C. albicans have a tight iron regulation system including 3 major transcriptional regulators, Sef1p, Sfu1p, and the Hap43p-associated CCAAT-binding complex.”
From The synthesis, regulation, and functions of sterols inCandida albicans: Well-known but still lots to learn (2016) · cites this paper as [82]
Deletion of SEF1, a transcription factor that regulates iron uptake, significantly attenuates C. albicans virulence in systemic infection models.
“deletion of SEF1, a transcription factor that regulates iron uptake, significantly attenuates virulence in systemic infection models (Chen et al. 2011).”
From Aloe emodin disrupts Candida albicans mitochondrial iron homeostasis against its hyphal development and oral candidiasis (2026) · cites this paper as Chen et al. 2011
All three genes Mrs4, Ccc1, and Smf3 are targets of regulation by Hap43.
“Importantly, all three of these genes are targets of regulation by Hap43 (Chen et al., 2011; Singh et al., 2011; Monteiro et al., 2017), linking regulation of iron not only to acquisition from external sources but also intracellular homeostasis.”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Chen et al., 2011
The Results sections on gene expression and DNA binding report that Hap43 regulates iron-homeostasis and iron-utilization genes, but the passages do not identify Mrs4, Ccc1, or Smf3 as targets. Searches for all three gene names, individually and together, found no passage establishing the specific claim. (LLM, conf=0.76)
Experimental — accuracy not yet measured

Iron concentration is a significant signal to induce morphological transformation in C. albicans.
“In addition, iron concentration is a signi fi cant signal to induce morphological transformation in C. albicans .”
From The synthesis, regulation, and functions of sterols inCandida albicans: Well-known but still lots to learn (2016) · cites this paper as [82]
The Results section on iron-level experiments reports effects on growth, while the Discussion describes regulation of iron uptake and utilization; neither links iron concentration to morphological transformation. Searches for morphological transformation, filamentation, yeast-to-hypha switching, and morphogenesis found no passage in our copy establishing the claimed signal. (LLM, conf=0.75)
Experimental — accuracy not yet measured
Iron serves as an important signal for some fungi during the transition from a commensal lifestyle to that of an invasive pathogen.
“Furthermore, iron serves as an important signal for some fungi during the transition from a commensal lifestyle to that of an invasive pathogen (Chen et al., 2011).”
From Iron in infection and immunity (2013) · cites this paper as Chen et al., 2011
Chen et al. studied how a transcriptional network in C. albicans evolved, with Sef1 joining an existing iron-responsive repressor system to control growth in distinct host niches.
“Chen et al. dissected the evolution of an elaborate transcriptional network in C. albicans whereby incorporation of a novel transcriptional activator, Sef1, into a pre-existing iron-responsive repressor system mediates growth in different host niches [90].”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [90]
Sef1 supports iron uptake and is required for virulence in living hosts.
“The authors demonstrated that Sef1 promotes iron acquisition and is essential for virulence in vivo.”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [90]
Sef1 and the repressor Sfu1 regulate each other.
“In addition, Sef1 is regulated by and itself regulates Sfu1, a transcriptional repressor.”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [90]
Sfu1 blocks iron uptake and is not needed for virulence, yet it is required for commensal growth in the gut.
“Sfu1 in turn represses iron acquisition and is dispensable for virulence, but is conversely essential for commensal growth in the gastrointestinal tract.”
From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [90]
Free iron availability in blood is very low (10−24 M Fe3+) and below the minimal concentration required for microbial growth (10−6 to 10−7 M Fe3+).
“Free iron availability is very low (10−24 M Fe3+) (19) and below the minimal concentration required for microbial growth (10−6 to 10−7 M Fe3+) (70).”
From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [19]
In C. albicans, Sef1 is a pivotal activator of iron uptake genes and plays an essential role during iron deficiency and for virulence in mice.
“In C. albicans, Sef1 is a pivotal activator of iron uptake genes and thus plays an essential role during iron deficiency and for virulence in mice (19).”
From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [19]

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Portrait of Candida albicans Adherence Regulators
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Iron - a key nexus in the virulence of Aspergillus fumigatus
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Candida parapsilosis Is a Significant Neonatal Pathogen: A Systematic Review and Meta-analysis
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Candida Survival Strategies
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Metabolism in fungal pathogenesis
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Candida albicans and Candida glabrata : global priority pathogens
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Candida albicans commensalism and pathogenicity are intertwined traits directed by a tightly knit transcriptional regulatory circuit
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Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen
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“albicans colonization (34), or a purified diet (PD) that does not require antibiotics (35).”
Background
HapX-Mediated Iron Homeostasis Is Essential for Rhizosphere Competence and Virulence of the Soilborne Pathogen Fusarium oxysporum
López‐Berges, M. S., Capilla, J., Turrà, D., Schafferer, L., Matthijs, S., Jöchl, C., Cornélis, P., Guarro, J., Haas, H., & Pietro, A. D. (2012) · The Plant Cell · doi:10.1105/tpc.112.098624 · Cited by 151 · see citing works
Candida albicans commensalism in the gastrointestinal tract
Neville, B. A., d’Enfert, C., & Bougnoux, M. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov081 · Cited by 139 · see citing works
Fungal iron homeostasis with a focus on Aspergillus fumigatus
Misslinger, M., Hortschansky, P., Brakhage, A. A., & Haas, H. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118885 · Cited by 134 · see citing works
Interspecies competition triggers virulence and mutability in Candida albicans – Pseudomonas aeruginosa mixed biofilms
Trejo-Hernández, A., Andrade-Domínguez, A., Hernández, M., & Encarnación, S. (2014) · The ISME Journal · doi:10.1038/ismej.2014.53 · Cited by 135 · see citing works
The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess
Gsaller, F., Hortschansky, P., Beattie, S. R., Klammer, V., Tuppatsch, K., Lechner, B. E., Rietzschel, N., Werner, E. R., Vogan, A. A., Chung, D., et al. (2014) · The EMBO Journal · doi:10.15252/embj.201489468 · Cited by 134 · see citing works
The synthesis, regulation, and functions of sterols inCandida albicans: Well-known but still lots to learn
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An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells
Tierney, L., Linde, J., Müller, S., Brunke, S., Molina, J. C., Hube, B., Schöck, U., Guthke, R., & Kuchler, K. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00085 · Cited by 128 · see citing works
Comparative Phenotypic Analysis of the Major Fungal Pathogens Candida parapsilosis and Candida albicans
Holland, L., Schröder, M., Turner, S. A., Taff, H. T., Andes, D. R., Grózer, Z., Gácser, A., Ames, L., Haynes, K., Higgins, D. G., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004365 · Cited by 132 · see citing works
Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase
Li, C. X., Gleason, J. E., Zhang, S. X., Bruno, V. M., Cormack, B. P., & Culotta, V. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1513447112 · Cited by 121 · see citing works
Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion
Pradhan, A., Avelar, G. M., Bain, J. M., Childers, D., Pelletier, C., Larcombe, D. E., Shekhova, E., Netea, M. G., Brown, G. D., Erwig, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13298-9 · Cited by 119 · see citing works
Iron at the Centre of Candida albicans Interactions
Fourie, R., Kuloyo, O. O., Mochochoko, B. M., Albertyn, J., & Pohl, C. H. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00185 · Cited by 118 · see citing works
Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy
Barber, M. F., & Elde, N. C. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.09.001 · Cited by 118 · see citing works
A Relay Network of Extracellular Heme-Binding Proteins Drives C. albicans Iron Acquisition from Hemoglobin
Kuznets, G., Vigonsky, E., Weissman, Z., Lalli, D., Gildor, T., Kauffman, S. J., Turano, P., Becker, J., Lewinson, O., & Kornitzer, D. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004407 · Cited by 118 · see citing works
Functional Genomic Analysis of Candida glabrata-Macrophage Interaction: Role of Chromatin Remodeling in Virulence
Rai, M. N., Balusu, S., Gorityala, N., Dandu, L., & Kaur, R. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002863 · Cited by 117 · see citing works
Current progress on pathogenicity‐related transcription factors in Fusarium oxysporum
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Innate immune responses against the fungal pathogen Candida auris
Wang, Y., Zou, Y., Chen, X., Li, H., Yin, Z., Zhang, B., Xu, Y., Zhang, Y., Zhang, R., Huang, X., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31201-x · Cited by 107 · see citing works
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Divergent Targets of Candida albicans Biofilm Regulator Bcr1 In Vitro and In Vivo
Fanning, S., Xu, W., Solis, N., Woolford, C. A., Filler, S. G., & Mitchell, A. P. (2012) · Eukaryotic Cell · doi:10.1128/ec.00103-12 · Cited by 106 · see citing works
Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation
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Candida albicans specializations for iron homeostasis: from commensalism to virulence
Noble, S. M. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.09.006 · Cited by 104 · see citing works
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Iron and copper as virulence modulators in human fungal pathogens
Ding, C., Festa, R. A., Sun, T., & Wang, Z. (2014) · Molecular Microbiology · doi:10.1111/mmi.12653 · Cited by 105 · see citing works
Yeast AP-1 like transcription factors (Yap) and stress response: a current overview
Rodrigues‐Pousada, C., Devaux, F., Caetano, S. M., Pimentel, C., da Silva, S. M., Gaspar‐Cordeiro, A., & Amaral, C. (2019) · Microbial Cell · doi:10.15698/mic2019.06.679 · Cited by 104 · see citing works
Candida albicans Interactions with Mucosal Surfaces during Health and Disease
Nikou, S.-A., Kichik, N., Brown, R., Ponde, N., Ho, J., Naglik, J., & Richardson, J. (2019) · Pathogens · doi:10.3390/pathogens8020053 · Cited by 103 · see citing works
Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi
Ries, L. N. A., Beattie, S. R., Cramer, R. A., & Goldman, G. H. (2017) · Molecular Microbiology · doi:10.1111/mmi.13887 · Cited by 99 · see citing works
The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice
Böhm, L., Torsin, S., Tint, S. H., Eckstein, M., Ludwig, T., & Pérez, J. C. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006699 · Cited by 95 · see citing works
Conserved and Divergent Roles of Bcr1 and CFEM Proteins in Candida parapsilosis and Candida albicans
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Fungi as Part of the Microbiota and Interactions with Intestinal Bacteria
Kapitan, M., Niemiec, M. J., Steimle, A., Frick, J.-S., & Jacobsen, I. D. (2018) · Current topics in microbiology and immunology · doi:10.1007/82_2018_117 · Cited by 93 · see citing works
Elevated catalase expression in a fungal pathogen is a double-edged sword of iron
Pradhan, A., Herrero-de-Dios, C. M., Belmonte, R. C., Budge, S., López, A., Kolmogorova, A., Lee, K. K., Martin, B. D., Ribeiro, A., Bebes, A., et al. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006405 · Cited by 91 · see citing works
Opportunistic yeast pathogens: reservoirs, virulence mechanisms, and therapeutic strategies
Polvi, E. J., Li, X., O’Meara, T. R., Leach, M. D., & Cowen, L. E. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1860-z · Cited by 90 · see citing works
A Histone Deacetylase Complex Mediates Biofilm Dispersal and Drug Resistance in Candida albicans
Nobile, C. J., Fox, E. P., Hartooni, N., Mitchell, K. F., Hnisz, D., Andes, D. R., Kuchler, K., & Johnson, A. D. (2014) · mBio · doi:10.1128/mbio.01201-14 · Cited by 87 · see citing works
“Not surprisingly, Sfu1, Crz2, and Nrg1 have been implicated in various aspects of biofilm formation; Sfu1 represses iron uptake genes and enhances commensalism in the gastrointestinal tract (18) and thus may play a role in biofilm formation on mucosal surfaces in the gut; Crz2 is required for the first step of biofilm…”
Background
Synergistic Regulation of Hyphal Elongation by Hypoxia, CO2, and Nutrient Conditions Controls the Virulence of Candida albicans
Lü, Y., Su, C., Solis, N. V., Filler, S. G., & Liu, H. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.10.008 · Cited by 87 · see citing works
Analysis of a fungus‐specific transcription factor family, the <scp>C</scp>andida albicans zinc cluster proteins, by artificial activation
Schillig, R., & Morschhäuser, J. (2013) · Molecular Microbiology · doi:10.1111/mmi.12327 · Cited by 85 · see citing works
Review article: fungal alterations in inflammatory bowel diseases
Lam, S., Zuo, T., Ho, M., Chan, F. K. L., Chan, P. K. S., & Ng, S. C. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15523 · Cited by 85 · see citing works
Normal Adaptation of Candida albicans to the Murine Gastrointestinal Tract Requires Efg1p-Dependent Regulation of Metabolic and Host Defense Genes
Pierce, J. V., Dignard, D., Whiteway, M. S., & Kumamoto, C. A. (2012) · Eukaryotic Cell · doi:10.1128/ec.00236-12 · Cited by 84 · see citing works
Post-transcriptional regulation of the Sef1 transcription factor controls the virulence of Candida albicans in its mammalian host
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RNA Enrichment Method for Quantitative Transcriptional Analysis of Pathogens In Vivo Applied to the Fungus Candida albicans
Amorim-Vaz, S., Tran, V. D. T., Pradervand, S., Pagni, M., Coste, A. T., & Sanglard, D. (2015) · mBio · doi:10.1128/mbio.00942-15 · Cited by 78 · see citing works
Commensalism and pathogenesis of Candida albicans at the mucosal interface
Schille, T. B., Sprague, J. L., Naglik, J. R., Brunke, S., & Hube, B. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-025-01174-x · Cited by 77 · see citing works
Beyond the wall:Candida albicanssecret(e)s to survive
Sorgo, A. G., Heilmann, C. J., Brul, S., de Koster, C. G., & Klis, F. M. (2012) · FEMS Microbiology Letters · doi:10.1111/1574-6968.12049 · Cited by 72 · see citing works
HapX, an Indispensable bZIP Transcription Factor for Iron Acquisition, Regulates Infection Initiation by Orchestrating Conidial Oleic Acid Homeostasis and Cytomembrane Functionality in Mycopathogen Beauveria bassiana
Peng, Y., Wang, J., Lin, H., Ding, J., Feng, M., & Ying, S. (2020) · mSystems · doi:10.1128/msystems.00695-20 · Cited by 72 · see citing works
Iron–sulfur cluster signaling: The common thread in fungal iron regulation
Gupta, M., & Outten, C. E. (2020) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2020.02.008 · Cited by 71 · see citing works
One population, multiple lifestyles: Commensalism and pathogenesis in the human mycobiome
Proctor, D. M., Drummond, R. A., Lionakis, M. S., & Segre, J. A. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.02.010 · Cited by 68 · see citing works
Commensal fungi in intestinal health and disease
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Dynamic Transcript Profiling of Candida albicans Infection in Zebrafish: A Pathogen-Host Interaction Study
Chen, Y. Y., Chao, C., Liu, F., Hsu, P., Chen, H.-F., Peng, S.-C., Chuang, Y., Lan, C., Hsieh, W., & Wong, D. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072483 · Cited by 64 · see citing works
Modeling the Transcriptional Regulatory Network That Controls the Early Hypoxic Response in Candida albicans
Sellam, A., van het Hoog, M., Tebbji, F., Beaurepaire, C., Whiteway, M., & Nantel, A. (2014) · Eukaryotic Cell · doi:10.1128/ec.00292-13 · Cited by 63 · see citing works
Verticillium dahliae CFEM proteins manipulate host immunity and differentially contribute to virulence
Wang, D., Zhang, D., Song, J., Li, J., Wang, J., Li, R., Klosterman, S. J., Kong, Z., Lin, F.-Z., Dai, X., et al. (2022) · BMC Biology · doi:10.1186/s12915-022-01254-x · Cited by 62 · see citing works
SRE1 Regulates Iron-Dependent and -Independent Pathways in the Fungal Pathogen Histoplasma capsulatum
Hwang, L. H., Seth, E. C., Gilmore, S. A., & Sil, A. (2011) · Eukaryotic Cell · doi:10.1128/ec.05274-11 · Cited by 60 · see citing works
Global proteomic analysis deciphers the mechanism of action of plant derived oleic acid against Candida albicans virulence and biofilm formation
Muthamil, S., Prasath, K. G., Priya, A., Precilla, P., & Pandian, S. K. (2020) · Scientific Reports · doi:10.1038/s41598-020-61918-y · Cited by 62 · see citing works
Iron alters the cell wall composition and intracellular lactate to affect Candida albicans susceptibility to antifungals and host immune response
Tripathi, A., Liverani, E., Tsygankov, A. Y., & Puri, S. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013413 · Cited by 56 · see citing works
In Vivo Systematic Analysis of Candida albicans Zn2-Cys6 Transcription Factors Mutants for Mice Organ Colonization
Vandeputte, P., Ischer, F., Sanglard, D., & Coste, A. T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026962 · Cited by 56 · see citing works
Identification of Genes Upregulated by the Transcription Factor Bcr1 That Are Involved in Impermeability, Impenetrability, and Drug Resistance of Candida albicans a/ α Biofilms
Srikantha, T., Daniels, K. J., Pujol, C., Kim, E., & Soll, D. R. (2013) · Eukaryotic Cell · doi:10.1128/ec.00071-13 · Cited by 54 · see citing works
Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health
Wasielewski, H., Alcock, J., & Aktipis, A. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13118 · Cited by 56 · see citing works
The Transcriptional Stress Response of Candida albicans to Weak Organic Acids
Cottier, F., Tan, A. S. M., Chen, J., Lum, J., Zolezzi, F., Poidinger, M., & Pavelka, N. (2015) · G3 Genes Genomes Genetics · doi:10.1534/g3.114.015941 · Cited by 54 · see citing works
Copper-only superoxide dismutase enzymes and iron starvation stress in Candida fungal pathogens
Schatzman, S. S., Peterson, R. L., Teka, M., He, B., Cabelli, D. E., Cormack, B. P., & Culotta, V. C. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011084 · Cited by 54 · see citing works
The Hap Complex in Yeasts: Structure, Assembly Mode, and Gene Regulation
Mao, Y., & Chen, C. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01645 · Cited by 51 · see citing works
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Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models
Amorim-Vaz, S., Delarze, E., Ischer, F., Sanglard, D., & Coste, A. T. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00367 · Cited by 53 · see citing works
Study of Candida albicans and its interactions with the host: A mini review
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Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis
Polvi, E. J., Averette, A. F., Lee, S. C., Kim, T., Bahn, Y., Veri, A. O., Robbins, N., Heitman, J., & Cowen, L. E. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006350 · Cited by 50 · see citing works
Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions
Hebecker, B., Vlaic, S., Conrad, T., Bauer, M. W., Brunke, S., Kapitan, M., Linde, J., Hube, B., & Jacobsen, I. D. (2016) · Scientific Reports · doi:10.1038/srep36055 · Cited by 52 · see citing works
Transcriptional Circuits Regulating Developmental Processes in Candida albicans
Rodríguez, D. L., Quail, M. M., Hernday, A. D., & Nobile, C. J. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.605711 · Cited by 53 · see citing works
Identification and Functional Characterization of Rca1, a Transcription Factor Involved in both Antifungal Susceptibility and Host Response in Candida albicans
Vandeputte, P., Pradervand, S., Ischer, F., Coste, A. T., Ferrari, S., Harshman, K., & Sanglard, D. (2012) · Eukaryotic Cell · doi:10.1128/ec.00134-12 · Cited by 51 · see citing works
Candida albicans possess a highly versatile and dynamic high‐affinity iron transport system important for its commensal‐pathogenic lifestyle
Mamouei, Z., Zeng, G., Wang, Y., & Wang, Y. (2017) · Molecular Microbiology · doi:10.1111/mmi.13864 · Cited by 49 · see citing works
Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis
Puri, S., Kumar, R., Rojas, I. G., Salvatori, O., & Edgerton, M. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02152-18 · Cited by 48 · see citing works
Fungal Metabolomics: A Comprehensive Approach to Understanding Pathogenesis in Humans and Identifying Potential Therapeutics
Alves, V., Zamith‐Miranda, D., Frasés, S., & Nosanchuk, J. D. (2025) · Journal of Fungi · doi:10.3390/jof11020093 · Cited by 48 · see citing works
Adaptation of Candida Albicans to Commensalism in the Gut
Prieto, D., Correia, I., Plá, J., & Román, E. (2016) · Future Microbiology · doi:10.2217/fmb.16.1 · Cited by 48 · see citing works
A fungal ABC transporter FgAtm1 regulates iron homeostasis via the transcription factor cascade FgAreA-HapX
Wang, Z., Ma, T., Huang, Y., Wang, J., Chen, Y., Kistler, H. C., Ma, Z., & Yin, Y. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007791 · Cited by 48 · see citing works
A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts
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Cellular iron homeostasis mediated by the Mrs4–Ccc1–Smf3 pathway is essential for mitochondrial function, morphogenesis and virulence in Candida albicans
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Adaptation to iron deficiency in human pathogenic fungi
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Heme-iron acquisition in fungi
Roy, U., & Kornitzer, D. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.05.006 · Cited by 44 · see citing works
A 5′ UTR ‐mediated translational efficiency mechanism inhibits the C andida albicans morphological transition
Childers, D. S., Mundodi, V., Banerjee, M., & Kadosh, D. (2014) · Molecular Microbiology · doi:10.1111/mmi.12576 · Cited by 45 · see citing works
Y ap7 is a transcriptional repressor of nitric oxide oxidase in yeasts, which arose from neofunctionalization after whole genome duplication
Merhej, J., Delaveau, T., Guitard, J., Palancade, B., Hennequin, C., Garcia, M., Lelandais, G., & Devaux, F. (2015) · Molecular Microbiology · doi:10.1111/mmi.12983 · Cited by 46 · see citing works
Systematic gene overexpression in Candida albicans identifies a regulator of early adaptation to the mammalian gut
Znaidi, S., van Wijlick, L., Hernández-Cervantes, A., Sertour, N., Desseyn, J., Vincent, F., Atanasova, R., Gouyer, V., Munro, C. A., Bachellier‐Bassi, S., et al. (2018) · Cellular Microbiology · doi:10.1111/cmi.12890 · Cited by 45 · see citing works
The Role of Fatty Acid Metabolites in Vaginal Health and Disease: Application to Candidiasis
Baldewijns, S., Sillen, M., Palmans, I., Vandecruys, P., Van Dijck, P., & Demuyser, L. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.705779 · Cited by 44 · see citing works
Novel role of the Candida albicans ferric reductase gene CFL1 in iron acquisition, oxidative stress tolerance, morphogenesis and virulence
Xu, N., Qian, K., Dong, Y., Chen, Y., Yu, Q., Zhang, B., Xing, L., & Li, M. (2014) · Research in Microbiology · doi:10.1016/j.resmic.2014.03.001 · Cited by 44 · see citing works
The Transcription Factor VdHapX Controls Iron Homeostasis and Is Crucial for Virulence in the Vascular Pathogen Verticillium dahliae
Wang, Y., Deng, C., Tian, L., Xiong, D., Tian, C., & Klosterman, S. J. (2018) · mSphere · doi:10.1128/msphere.00400-18 · Cited by 44 · see citing works
Emerging Mechanisms of Drug Resistance in Candida albicans
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The protein kinase Ire1 impacts pathogenicity of <scp> Candida albicans </scp> by regulating homeostatic adaptation to endoplasmic reticulum stress
Sircaik, S., Román, E., Bapat, P., Lee, K. K., Andes, D. R., Gow, N. A. R., Nobile, C. J., Pla, J., & Panwar, S. L. (2021) · Cellular Microbiology · doi:10.1111/cmi.13307 · Cited by 41 · see citing works
Novel insight into the expression and function of the multicopper oxidases in Candida albicans
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Iron restriction-induced adaptations in the wall proteome of Candida albicans
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Self-citation
Candida albicans specializations for iron homeostasis: from commensalism to virulence
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Regulatory networks affected by iron availability in Candida albicans
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Authors: Chen, C., Pande, K., French, S. D., Tuch, B. B., & Noble, S. M.
Affiliations: University of California, San Francisco (US)
Amgen (United States) (US)
Corresponding author: Noble, Suzanne M.
ORCID: Chen, Changbin
Pande, Kalyan
Noble, Suzanne M.
Venue: Cell Host & Microbe
Publisher: Elsevier BV
Published: 2011-08
Volume: 10
Issue: 2
Pages: 118-135
ISSN: 1931-3128 (ISSN-L)
DOI: 10.1016/j.chom.2011.07.005
PMC: PMC3165008
OpenAlex: W1985155016
Semantic Scholar: 52ed5b255961f91a7cd1567abaee77befa608f08
Cited by: 314
References: 61
Citations by year: 2026: 12 · 2025: 25 · 2024: 22 · 2023: 22 · 2022: 21 · 2021: 28 · 2020: 29 · 2019: 27 · 2018: 17 · 2017: 20 · 2016: 17 · 2015: 15 · 2014: 16 · 2013: 22 · 2012: 17
FWCI: 7.65
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 752 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Host & Microbe (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Allergy and Infectious Diseases (KO8AI062800, K08AI062800)
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 › Epidemiology › Fungal Infections and Studies
Keywords: Candida albicans, iron homeostasis, iron absorption, transcriptional regulation, commensalism, virulence, bloodstream infection, iron toxicity
MeSH terms: Alleles, Animals, Candida albicans, Female, Fungal Proteins, Homeostasis, Humans, Iron, Mice, Inbred BALB C, Phylogeny, Plasma, Promoter Regions, Genetic, Repressor Proteins, Saccharomyces cerevisiae, Symbiosis, Transcription Factors, Transcription, Genetic, Virulence, Transcriptional Activation, Gene Expression Regulation, Fungal, Chromatin Immunoprecipitation, Mice

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An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis

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