Candida albicans reprioritizes metal handling during fluconazole stress

Hunsaker, Elizabeth W.; Franz, Katherine J.

doi:10.1039/c9mt00228f

Cited by 22Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

Candida albicans reprioritizes metal handling during fluconazole stress

Open access

Hunsaker, Elizabeth W., Franz, Katherine J.·2019·Metallomics

DOI 10.1039/c9mt00228fPMC PMC6927248

Open this paper in CoChat — free account

Abstract

Fluconazole stress pushes C. albicans outside of metal homeostasis, requiring adaptation. Fungal adaptation to drug stress requires remodeling of metal homeostasis networks, creating vulnerabilities to environmental fluctuations in Cu availability.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1039/c9mt00228f

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Increased intracellular iron in fluconazole-treated C. albicans cells was not retained in labile pools and instead was incorporated into structures not observable by electron paramagnetic resonance.
“A previous study showed that the increased intracellular iron in fluconazole-treated C. albicans cells was not retained in labile pools and instead was incorporated into structures not observable by electron paramagnetic resonance (30).”
From Candida albicans enhances iron uptake to maintain fluconazole resistance (2025) · cites this paper as [30]
The Results section (‘Fluconazole depletes EPR-detectable Fe’) reports that fluconazole increased total iron while reducing the EPR-detectable iron signal. It says this *suggests* the additional iron is not held in labile pools but incorporated into EPR-invisible structures; the citing sentence presents that interpretation as established fact. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Elevated iron levels are redistributed for the production of very specific iron-related proteins.
“In line with the previous findings (30), this suggests that elevated iron levels are redistributed for the production of very specific iron-related proteins.”
From Candida albicans enhances iron uptake to maintain fluconazole resistance (2025) · cites this paper as [30]
C. albicans reprioritizes metal handling during fluconazole stress, including that for iron.
“C. albicans reprioritizes metal handling during fluconazole stress, including that for iron (30).”
From Candida albicans enhances iron uptake to maintain fluconazole resistance (2025) · cites this paper as [30]
MAPK Cek1 activation can impact sensitivity towards tunicamycin and CFW.
“Mitogen activated protein kinase (MAPK) Cek1 activation can impact sensitivity towards tunicamycin and CFW [39,40]”
From High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis (2022) · cites this paper as [39]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity
Macomber, L., & Imlay, J. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812808106 · Cited by 1,117 · see citing works
Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species
Whaley, S. G., Berkow, E. L., Rybak, J. M., Nishimoto, A. T., Barker, K. S., & Rogers, P. D. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02173 · Cited by 900 · see citing works
Tackling Human Fungal Infections
Brown, G. D., Denning, D. W., & Levitz, S. M. (2012) · Science · doi:10.1126/science.1222236 · Cited by 619 · see citing works
Strains and Strategies for Large-Scale Gene Deletion Studies of the Diploid Human Fungal Pathogen Candida albicans
Noble, S. M., & Johnson, A. D. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.2.298-309.2005 · Cited by 592 · see citing works
A Phenotypic Profile of the Candida albicans Regulatory Network
Homann, O. R., Dea, J., Noble, S. M., & Johnson, A. D. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000783 · Cited by 444 · see citing works
The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens
Djoko, K. Y., Ong, C.-L. Y., Walker, M. J., & McEwan, A. G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.647099 · Cited by 417 · see citing works
Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae
MacDiarmid, C. W., Gaither, L. A., & Eide, D. (2000) · The EMBO Journal · doi:10.1093/emboj/19.12.2845 · Cited by 389 · see citing works
The Fungal Genetics Stock Center: a repository for 50 years of fungal genetics research
McCluskey, K., Wiest, A. E., & Plamann, M. D. (2010) · Journal of Biosciences · doi:10.1007/s12038-010-0014-6 · Cited by 319 · see citing works
An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis
Chen, C., Pande, K., French, S. D., Tuch, B. B., & Noble, S. M. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.07.005 · Cited by 314 · see citing works
Copper tolerance and virulence in bacteria
Ladomersky, E., & Petris, M. J. (2015) · Metallomics · doi:10.1039/c4mt00327f · Cited by 280 · see citing works
Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia
Rosenberg, A., Ene, I. V., Bibi, M., Zakin, S., Segal, E. S., Ziv, N., Dahan, A. M., Colombo, A. L., Bennett, R. J., & Berman, J. (2018) · Nature Communications · doi:10.1038/s41467-018-04926-x · Cited by 270 · see citing works
Upregulation of ERG Genes in Candida Species by Azoles and Other Sterol Biosynthesis Inhibitors
Henry, K. W., Nickels, J. T., & Edlind, T. D. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.10.2693-2700.2000 · Cited by 216 · see citing works
The Yin and Yang of copper during infection
Besold, A. N., Culbertson, E. M., & Culotta, V. C. (2016) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-016-1335-1 · Cited by 215 · see citing works
Transition Metal Sequestration by the Host-Defense Protein Calprotectin
Zygiel, E. M., & Nolan, E. M. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012312 · Cited by 187 · see citing works
Carbon source‐induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen <scp> C </scp> andida albicans
Ene, I. V., Heilmann, C. J., Sorgo, A. G., Walker, L. A., de Koster, C. G., Munro, C. A., Klis, F. M., & Brown, A. J. P. (2012) · Proteomics · doi:10.1002/pmic.201200228 · Cited by 159 · see citing works
The high copper tolerance of Candida albicans is mediated by a P-type ATPase
Weissman, Z., Berdicevsky, I., Cavari, B., & Kornitzer, D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3520 · Cited by 152 · see citing works
Succinylacetone, a potent inhibitor of heme biosynthesis: Effect on cell growth, heme content and δ-aminolevulinic acid dehydratase activity of malignant murine erythroleukemia cells
Ebert, P. S., Hess, R. A., Frykholm, B. C., & Tschudy, D. P. (1979) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(79)91133-1 · Cited by 151 · see citing works
Unexpected Link between Iron and Drug Resistance of Candida spp.: Iron Depletion Enhances Membrane Fluidity and Drug Diffusion, Leading to Drug-SusceptibleCells
Prasad, T., Chandra, A., Mukhopadhyay, C. K., & Prasad, R. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00653-06 · Cited by 149 · see citing works
Yeast lacking superoxide dismutase (s) show elevated levels of “free iron” as measured by whole cell electron paramagnetic resonance
Srinivasan, C., Liba, A., Imlay, J. A., Valentine, J. S., & Gralla, E. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004239200 · Cited by 134 · see citing works
Regulation of the Hypoxic Response in Candida albicans
Synnott, J. M., Guida, A., Mulhern-Haughey, S., Higgins, D. G., & Butler, G. (2010) · Eukaryotic Cell · doi:10.1128/ec.00159-10 · Cited by 132 · see citing works
Candida albicans Expresses an Unusual Cytoplasmic Manganese-containing Superoxide Dismutase (SOD3 Gene Product) upon the Entry and during the Stationary Phase
Lamarre, C., LeMay, J.-D., Deslauriers, N., & Bourbonnais, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108095200 · Cited by 123 · see citing works
Role of divalent metals in infectious disease susceptibility and outcome
Weiss, G., & Carver, P. L. (2018) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2017.01.018 · Cited by 123 · 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
Essential metals at the host-pathogen interface: nutritional immunity and micronutrient assimilation by human fungal pathogens
Crawford, A., & Wilson, D. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov071 · Cited by 120 · see citing works
Potent Synergistic Effect of Doxycycline with Fluconazole against Candida albicans Is Mediated by Interference with Iron Homeostasis
Fiori, A., & Van Dijck, P. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06017-11 · Cited by 112 · see citing works
A multicopper oxidase gene from Candida albicans: cloning, characterization and disruption b bThe EMBL accession number for the sequence reported in this paper is Y09329.
Eck, R., Hundt, S. M., Härtl, A., Roemer, E., & Künkel, W. (1999) · Microbiology · doi:10.1099/00221287-145-9-2415 · Cited by 109 · see citing works
Cell wall-related bionumbers and bioestimates of Saccharomyces cerevisiae and Candida albicans
Klis, F. M., de Koster, C. G., & Brul, S. (2014) · Eukaryotic Cell · doi:10.1128/ec.00250-13 · Cited by 109 · see citing works
Emerging Opportunities To Manipulate Metal Trafficking for Therapeutic Benefit
Hunsaker, E. W., & Franz, K. J. (2019) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.9b01029 · Cited by 106 · see citing works
Self-citation
Activation and Alliance of Regulatory Pathways in C. albicans during Mammalian Infection
Xu, W., Solis, N. V., Ehrlich, R. L., Woolford, C. A., Filler, S. G., & Mitchell, A. P. (2015) · PLOS Biology · doi:10.1371/journal.pbio.1002076 · Cited by 103 · see citing works
Metals in infectious diseases and nutritional immunity
Skaar, E. P., & Raffatellu, M. (2015) · Metallomics · doi:10.1039/c5mt90021b · Cited by 101 · see citing works
Copper at the Fungal Pathogen-Host Axis
García‐Santamarina, S., & Thiele, D. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.649129 · Cited by 98 · see citing works
Evaluation of Differential Gene Expression in Fluconazole-Susceptible and -Resistant Isolates of Candida albicans by cDNA Microarray Analysis
Rogers, P. D., & Barker, K. S. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.11.3412-3417.2002 · Cited by 96 · see citing works
Exploiting Innate Immune Cell Activation of a Copper-Dependent Antimicrobial Agent during Infection
Festa, R. A., Helsel, M. E., Franz, K. J., & Thiele, D. J. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.06.009 · Cited by 94 · see citing works
Self-citation
Analysis of iron–sulfur protein maturation in eukaryotes
Pierik, A. J., Netz, D. J. A., & Lill, R. (2009) · Nature Protocols · doi:10.1038/nprot.2009.39 · Cited by 94 · see citing works
Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal
Correia, M. A., Sinclair, P. R., & Matteis, F. D. (2010) · Drug Metabolism Reviews · doi:10.3109/03602532.2010.515222 · Cited by 88 · see citing works
UPC2 Is Universally Essential for Azole Antifungal Resistance in Candida albicans
Vasicek, E. M., Berkow, E. L., Flowers, S. A., Barker, K. S., & Rogers, P. D. (2014) · Eukaryotic Cell · doi:10.1128/ec.00221-13 · Cited by 71 · see citing works
POPULATION STUDIES IN MICROORGANISMS I. EVOLUTION OF DIPLOIDY IN SACCHAROMYCES CEREVISIAE
Adams, J., & Hansche, P. E. (1974) · Genetics · doi:10.1093/genetics/76.2.327 · Cited by 71 · see citing works
Biphasic zinc compartmentalisation in a human fungal pathogen
Crawford, A., Lehtovirta‐Morley, L. E., Alamir, O., Niemiec, M. J., Alawfi, B. S., Alsarraf, M., Skrahina, V., Costa, A. C. B. P., Anderson, A., Yellagunda, S., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007013 · Cited by 68 · see citing works
The Candida albicans CTR1 gene encodes a functional copper transporter
Marvin, M. E., WILLIAMS, P. H., & Cashmore, A. M. (2003) · Microbiology · doi:10.1099/mic.0.26172-0 · Cited by 67 · see citing works
Antimicrobial Action of Copper Is Amplified via Inhibition of Heme Biosynthesis
Djoko, K. Y., & McEwan, A. G. (2013) · ACS Chemical Biology · doi:10.1021/cb4002443 · Cited by 66 · see citing works
Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events
Potrykus, J., Stead, D., MacCallum, D. M., Urgast, D. S., Raab, A., van Rooijen, N., Feldmann, J., & Brown, A. J. P. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003676 · Cited by 66 · see citing works
Phosphate is the third nutrient monitored by TOR in Candida albicans and provides a target for fungal-specific indirect TOR inhibition
Liu, N.-N., Flanagan, P. R., Zeng, J., Jani, N. M., Cardenas, M. E., Moran, G. P., & Köhler, J. R. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617799114 · Cited by 62 · see citing works
The roles of zinc and copper sensing in fungal pathogenesis
Ballou, E. R., & Wilson, D. (2016) · Current Opinion in Microbiology · doi:10.1016/j.mib.2016.05.013 · Cited by 61 · see citing works
The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1
Marvin, M. E., Mason, R. P., & Cashmore, A. M. (2004) · Microbiology · doi:10.1099/mic.0.27004-0 · Cited by 60 · see citing works
Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections
Mackie, J., Szabo, E. K., Urgast, D. S., Ballou, E. R., Childers, D. S., MacCallum, D. M., Feldmann, J., & Brown, A. J. P. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158683 · Cited by 60 · see citing works
Iron Content of Saccharomyces cerevisiae Cells Grown under Iron-Deficient and Iron-Overload Conditions
Holmes‐Hampton, G. P., Jhurry, N. D., McCormick, S. P., & Lindahl, P. A. (2012) · Biochemistry · doi:10.1021/bi3015339 · Cited by 56 · see citing works
Cryptococcus neoformans Iron-Sulfur Protein Biogenesis Machinery Is a Novel Layer of Protection against Cu Stress
García‐Santamarina, S., Uzarska, M. A., Festa, R. A., Lill, R., & Thiele, D. J. (2017) · mBio · doi:10.1128/mbio.01742-17 · Cited by 54 · see citing works
A defect in iron uptake enhances the susceptibility of Cryptococcus neoformans to azole antifungal drugs
Kim, J., Cho, Y.-J., Do, E., Choi, J., Hu, G., Cadieux, B., Chun, J., Lee, Y., Kronstad, J. W., & Jung, W. H. (2012) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2012.08.006 · Cited by 53 · see citing works
Iron Restriction to Clinical Isolates of Candida albicans by the Novel Chelator DIBI Inhibits Growth and Increases Sensitivity to AzolesIn VitroandIn Vivoin a Murine Model of Experimental Vaginitis
Savage, K. A., Parquet, M. D. C., Allan, D. S., Davidson, R. J., Holbein, B. E., Lilly, E. A., & Fidel, P. L. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02576-17 · Cited by 53 · see citing works
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
Fluconazole induces ROS in Cryptococcus neoformans and contributes to DNA damage in vitro
Peng, C. A., Gaertner, A. A. E., Henriquez, S. A., Fang, D., Colón-Reyes, R. J., Brumaghim, J. L., & Kozubowski, L. (2018) · PLoS ONE · doi:10.1371/journal.pone.0208471 · Cited by 45 · see citing works
Mössbauer and EPR Study of Iron in Vacuoles from Fermenting Saccharomyces cerevisiae
Cockrell, A. L., Holmes‐Hampton, G. P., McCormick, S. P., Chakrabarti, M., & Lindahl, P. A. (2011) · Biochemistry · doi:10.1021/bi2014954 · Cited by 44 · see citing works
An Adaptation to Low Copper in Candida albicans Involving SOD Enzymes and the Alternative Oxidase
Broxton, C. N., & Culotta, V. C. (2016) · PLOS ONE · doi:10.1371/journal.pone.0168400 · Cited by 41 · see citing works
Heme bioavailability and signaling in response to stress in yeast cells
Hanna, D. A., Hu, R., Kim, H.-J., Martinez-Guzman, O., Torres, M. P., & Reddi, A. R. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002125 · Cited by 39 · see citing works
RNA sequencing revealed novel actors of the acquisition of drug resistance in Candida albicans
Dhamgaye, S., Bernard, M., Lelandais, G., Sismeiro, O., Lemoine, S., Coppée, J., Crom, S. L., Prasad, R., & Devaux, F. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-396 · Cited by 36 · see citing works
Mitochondrial Cochaperone Mge1 Is Involved in Regulating Susceptibility to Fluconazole in Saccharomyces cerevisiae and Candida Species
Demuyser, L., Swinnen, E., Fiori, A., Herrera-Malaver, B., Verstrepen, K., & Van Dijck, P. (2017) · mBio · doi:10.1128/mbio.00201-17 · Cited by 33 · see citing works
cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients
Xu, Z. Q., Zhang, L., Zhang, J., Cao, Y., Yu, Y.-Y., Wang, D., Ying, K., Chen, W., & Jiang, Y. (2006) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2006.03.004 · Cited by 30 · see citing works
A copper hyperaccumulation phenotype correlates with pathogenesis in Cryptococcus neoformans
Raja, M. R., Waterman, S. R., Qiu, J. F., Bleher, R., Williamson, P. R., & O’Halloran, T. V. (2013) · Metallomics · doi:10.1039/c3mt20220h · Cited by 24 · see citing works
Copper potentiates azole antifungal activity in a way that does not involve complex formation
Hunsaker, E. W., & Franz, K. J. (2019) · Dalton Transactions · doi:10.1039/c9dt00642g · Cited by 23 · see citing works
Self-citation
Activity of fluconazole and its Cu(II) complex towards Candida species
Ząbek, A., Nagaj, J., Grabowiecka, A., Dworniczek, E., Nawrot, U., Młynarz, P., & Jeżowska‐Bojczuk, M. (2014) · Medicinal Chemistry Research · doi:10.1007/s00044-014-1275-7 · Cited by 13 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Whaley, 2016, Front. Microbiol., 7, 2173

Sorted by citations

Transcriptome Analysis Uncovers a Link Between Copper Metabolism, and Both Fungal Fitness and Antifungal Sensitivity in the Opportunistic Yeast Candida albicans
Khemiri, I., Tebbji, F., & Sellam, A. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00935 · Cited by 40 · see citing works
“However, a recent study had shown that ergosterol depletion by fluconazole do not affect the intracellular amount of Cu in C. albicans (Hunsaker and Franz, 2019).”
Background
Copper Acts Synergistically With Fluconazole in Candida glabrata by Compromising Drug Efflux, Sterol Metabolism, and Zinc Homeostasis
Gaspar‐Cordeiro, A., Amaral, C., Pobre, V., Antunes, W., Petronilho, A., Paixão, P., Matos, A., & Pimentel, C. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.920574 · Cited by 16 · see citing works
High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis
Tripathi, A., Nahar, A., Sharma, R., Kanaskie, T., Al-Hebshi, N., & Puri, S. (2022) · Journal of Oral Microbiology · doi:10.1080/20002297.2022.2044110 · Cited by 16 · see citing works
“albicans causes extensive remodeling of iron homeostasis networks [38] that may limit the actual changes in intracellular iron levels caused by growth in low and high iron.”
Background
Role of the high-affinity reductive iron acquisition pathway of Candida albicans in prostaglandin E2 production, virulence, and interaction with Pseudomonas aeruginosa
Mochochoko, B. M., Ezeokoli, O. T., Sebolai, O. M., Albertyn, J., & Pohl, C. H. (2021) · Medical Mycology · doi:10.1093/mmy/myab015 · Cited by 14 · see citing works
Resurgence and Repurposing of Antifungal Azoles by Transition Metal Coordination for Drug Discovery
Cortat, Y., & Zobi, F. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15102398 · Cited by 14 · see citing works
Copper Availability Influences the Transcriptomic Response of Candida albicans to Fluconazole Stress
Hunsaker, E. W., Yu, C.-H. A., & Franz, K. J. (2021) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkab065 · Cited by 13 · see citing works
Self-citation
Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans
Hunsaker, E. W., McAuliffe, K. J., & Franz, K. J. (2020) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-020-01796-x · Cited by 9 · see citing works
Self-citation
Candida albicans enhances iron uptake to maintain fluconazole resistance
Sharma, R., Nahar, A., & Puri, S. (2025) · Infection and Immunity · doi:10.1128/iai.00002-25 · Cited by 8 · see citing works
Sustainable biosynthesis of silver nanoparticles from Gmelina arborea: Photocatalytic, in vitro biological implications, and in silico analysis for microbial metalloproteins
Thakar, M. S., Trivedi, P. G., & Sindhav, G. M. (2025) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2025.126966 · Cited by 8 · see citing works
New anticandidal Cu( i ) complexes with neocuproine and ketoconazole derived diphenyl(aminomethyl)phosphane: luminescence properties for detection in fungal cells
Starosta, R., de Almeida, R. F. M., Puchalska, M., Białońska, A., Panek, J. J., Jezierska, A., Szmigiel, I., Suchodolski, J., & Krasowska, A. (2020) · Dalton Transactions · doi:10.1039/d0dt01162b · Cited by 8 · see citing works
Regulation of copper uptake by the SWI/SNF chromatin remodeling complex in Candida albicans affects susceptibility to antifungal and oxidative stresses under hypoxia
Khemiri, I., Tebbji, F., Burgain, A., & Sellam, A. (2024) · FEMS Yeast Research · doi:10.1093/femsyr/foae018 · Cited by 6 · see citing works
“We and others hav e pr e viousl y shown that Cu homeostasis modulates antifungal tolerance in C. albicans (Hunsaker and Franz 2019 , Khemiri et al. 2020 ).”
The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance in Candida albicans
Druseikis, M. E., Mottola, A., & Berman, J. G. (2023) · Current Clinical Microbiology Reports · doi:10.1007/s40588-023-00189-3 · Cited by 5 · see citing works
“Connections between iron, sterol biosynthesis, and ER activity abound: (1) Erg11 requires the iron-containing metalloporphyrin cofactor heme to function, and (2) the inhibition of ergosterol biosynthesis affects ER activity, and (3) fluconazole treatment rapidly causes the incorporation of free iron into structures su…”
Background
Association between pica practice, oral health, and cariogenic microorganisms of US pregnant women: A cross-sectional study
Wu, Y., Xiao, J., Rashwan, N., Morrissey, A., Yousif, D., Jallad, N. A., Fiscella, K. A., Wu, T., & Abu, B. A. Z. (2025) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2025.106277 · Cited by 4 · see citing works
A chemically induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development
Bose, S., Sahu, S. R., Dutta, A., & Acharya, N. (2024) · eLife · doi:10.7554/elife.93760 · Cited by 4 · see citing works
Bidentate Metal-Binding Motifs in US FDA Approved Small Molecule Drugs
Njardarson, J. T., & Tomat, E. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01319 · Cited by 3 · see citing works
Prochelators modulate azole activity against Candida albicans in a metal-dependent manner
Merriman, M. A., Denning-Jannace, C. A., Hurtado, A. B., Vaccaro, F. A., Sung, Y., Tomat, E., & Franz, K. J. (2026) · RSC Chemical Biology · doi:10.1039/d6cb00073h · Cited by 2 · see citing works
“17–20 These observations underscore the intimate connection between metal-dependent processes and antifungal susceptibility.”
InfluentialSelf-citation
A chemically-induced attenuated strain of Candida albicans generates robust protective immune response and prevents systemic candidiasis developmentPreprint
Bose, S., Sahu, S. R., Dutta, A., & Acharya, N. (2024) · eLife · doi:10.7554/elife.93760.1
Leveraging Vulnerabilities in Copper Trafficking for Synergistic Antifungal Activity
Denning-Jannace, C. A., James, K. J., Ortiz, C. M., Sturrock, G. R., Robison, A. T. R., Vaccaro, F. A., Kuhn, S. A., Fitzgerald, M. C., & Franz, K. J. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.5c00525
Self-citation
Isw2-mediated chromatin remodeling governs antifungal tolerance and heteroresistance in Candida albicansPreprint
Mantilla, M. J., Tebbji, F., Vincent, A. T., Villeneuve, L. R., Chatr‐aryamontri, A., & Sellam, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.21.719916
In Vivo Evaluation of a Nanoemulsion-Delivered Chromium(III)–Triazole Complex Against Fluconazole-Resistant Candida albicans
Bedoya-Florez, M.-V., Murcia-Galán, R. A., Roa-Cordero, M. V., Pinto, S. M. L., Puerta-Arias, J. D., Alvarez-Ricardo, Y., Hurtado, J., & Naranjo, T. W. (2026) · Journal of Fungi · doi:10.3390/jof12060403
“Possible explanations include differences in membrane composition or cellular stress responses, as previously described in Candida [26–29].”
Oxidative stress responses in human fungal pathogens: a review of molecular mechanisms
Pereira, M. D., Costa, L. D. R., Mattos, L. M. M., Pires, D. C., Fonseca, F. L., Santos, A. L. S., & Riger, C. J. (2026) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2026.2706136

Efficacy of CS-758, a Novel Triazole, against Experimental Fluconazole-Resistant Oropharyngeal Candidiasis in Mice
Kamai, Y., Kubota, M., Fukuoka, T., Kamai, Y., Maeda, N., Hosokawa, T., Shibayama, T., Uchida, K., Yamaguchi, H., & Kuwahara, S. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.2.601-606.2003 · Cited by 9 · see citing works
Stability of complexes of Fluconazole and other four antibiotics
Jin, W. (2004) · Di-Si Junyi Daxue xuebao
Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail
Rich, P. A., Scher, R. K., Breneman, D., Savin, R. C., Feingold, D. S., Konnikov, N., Shupack, J. L., Pinnell, S. R., Levine, N. S., Lowe, N. J., et al. (1998) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(98)70493-1 · Cited by 41 · see citing works
Fluconazole-resistant Candida species in the oral flora of fluconazole-exposed HIV-positive patients
Hunter, K. D., Gibson, J. A. G., Lockhart, P. B., et al. (1998) · Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology · doi:10.1016/s1079-2104(98)90291-8 · Cited by 45 · see citing works
[Fluconazole in meningeal coccidioidomycosis].
Jj, A.-G., Ba, C.-C., Ja, P. Z., et al. (1997) · PubMed · Cited by 4 · see citing works

Authors: Hunsaker, E. W., & Franz, K. J.
Affiliations: Duke University (US)
Corresponding author: Franz, Katherine J.
ORCID: Hunsaker, Elizabeth W.
Franz, Katherine J.
Venue: Metallomics
Publisher: Oxford University Press (OUP)
Published: 2019
Volume: 11
Issue: 12
Pages: 2020-2032
ISSN: 1756-5901 (ISSN-L)
1756-591X
DOI: 10.1039/c9mt00228f
PMC: PMC6927248
OpenAlex: W2983505262
Cited by: 22
References: 60
Citations by year: 2026: 6 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3
FWCI: 0.58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: rsc.li/journals-terms-of-use (am, 673 d)
Locations: Metallomics (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (GM084176)
U.S. Department of Education (P200A150114)
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, metal homeostasis, fluconazole, copper imports, iron mobilization, manganese, zinc, ergosterol biosynthesis, heme biosynthesis, antifungal resistance, fungal adaptation, metal cofactors
MeSH terms: Adaptation, Physiological, Antifungal Agents, Candida albicans, Ergosterol, Homeostasis, Metals, Microbial Sensitivity Tests, Fluconazole, Drug Resistance, Fungal, Biosynthetic Pathways

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Candida albicans reprioritizes metal handling during fluconazole stress

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks