Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence
Open accessAbstract
Copper (Cu) is an essential metal that is toxic at high concentrations. Thus, pathogens often rely on host Cu for growth, but host cells can hyperaccumulate Cu to exert antimicrobial effects. The human fungal pathogen Cryptococcus neoformans encodes many Cu-responsive genes, but their role in infection is unclear. We determined that pulmonary C. neoformans infection results in Cu-specific induction of genes encoding the Cu-detoxifying metallothionein (Cmt) proteins. Mutant strains lacking CMTs or expressing Cmt variants defective in Cu-coordination exhibit severely attenuated virulence and reduced pulmonary colonization. Consistent with the upregulation of Cmt proteins, C. neoformans pulmonary infection results in increased serum Cu concentrations and increases and decreases alveolar macrophage expression of the Cu importer (Ctr1) and ATP7A, a transporter implicated in phagosomal Cu compartmentalization, respectively. These studies indicate that the host mobilizes Cu as an innate antifungal defense but C. neoformans senses and neutralizes toxic Cu to promote infection.
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
Cites
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?
The CTR4-2p-HSP90 mutant displays significantly attenuated virulence relative to the wild-type control upon intranasal inoculation.
“we observed significantly attenuated virulence for this mutant relative to the wild-type control upon intranasal inoculation (Figure 4F)”
From Genetic analysis of Hsp90 function in <i>Cryptococcus neoformans</i> highlights key roles in stress tolerance and virulence (2022) · cites this paper as Ding et al. 2013
Copper concentrations vary widely in different tissues within a mammalian host.
“the copper transporter gene CTR4 is expressed by C. neoformans at a constant low level in fungus growing in the lungs of mice, but is expressed at a high level in fungus isolated from the central nervous system due to the different physiological copper concentrations present at these sites (Steen et al. 2003; Ding et al. 2013).”
From Genetic analysis of Hsp90 function in <i>Cryptococcus neoformans</i> highlights key roles in stress tolerance and virulence (2022) · cites this paper as Ding et al. 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
[1] Role of free radicals and catalytic metal ions in human disease: An overview
Halliwell, B., & Gutteridge, J. M. C. (1990) · Methods in Enzymology · doi:10.1016/0076-6879(90)86093-b · Cited by 4,994 · see citing works
Hamer, D. H. (1986) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.55.070186.004405 · Cited by 1,655 · see citing works
Nutritional immunity: transition metals at the pathogen–host interface
Hood, M. I., & Skaar, E. P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2836 · Cited by 1,535 · see citing works
Nathan, C., & Shiloh, M. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.8841 · Cited by 1,469 · see citing works
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
The importance of free radicals and catalytic metal ions in human diseases.
Halliwell, B., & Gutteridge, J. M. C. (1985) · Molecular Aspects of Medicine · doi:10.1016/0098-2997(85)90001-9 · Cited by 941 · see citing works
Dancis, A., Yuan, D. S., Haile, D., Askwith, C., Eide, D., Moehle, C., Kaplan, J., & Klausner, R. D. (1994) · Cell · doi:10.1016/0092-8674(94)90345-x · Cited by 659 · see citing works
A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity
White, C., Lee, J., Kambe, T., Fritsche, K., & Petris, M. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.070201 · Cited by 524 · see citing works
Wagner, D., Maser, J. M., Lai, B. C. H., Cai, Z., Barry, C. E., zu Bentrup, K. H., Russell, D. G., & Bermudez, L. E. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.3.1491 · Cited by 430 · see citing works
Effect of the laccase gene CNLAC1, on virulence of Cryptococcus neoformans.
Salas, S. D., Bennett, J. E., Kwon-Chung, K. J., Perfect, J. R., & Williamson, P. R. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.2.377 · Cited by 405 · see citing works
Williamson, P. R. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.3.656-664.1994 · Cited by 371 · see citing works
Oxygen‐induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS
Furukawa, Y., Torres, A. S., & O’Halloran, T. V. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600276 · Cited by 369 · see citing works
Macomber, L., Rensing, C., & Imlay, J. A. (2007) · Journal of Bacteriology · doi:10.1128/jb.01357-06 · Cited by 356 · see citing works
Cryptococcal cell morphology affects host cell interactions and pathogenicity
Okagaki, L. H., Strain, A. K., Nielsen, J. N., Charlier, C., Baltes, N. J., Chrétien, F., Heitman, J., Dromer, F., & Nielsen, K. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000953 · Cited by 345 · see citing works
Self-citationExpanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box
Kronstad, J. W., Attarian, R., Cadieux, B., Choi, J., D’Souza, C. A., Griffiths, E., Geddes, J. M. H., Hu, G., Jung, W. H., Kretschmer, M., et al. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2522 · Cited by 340 · see citing works
Copper resistance is essential for virulence of <i>Mycobacterium tuberculosis</i>
Wolschendorf, F., Ackart, D., Shrestha, T. B., Hascall-Dove, L., Nolan, S., Lamichhane, G., Wang, Y., Bossmann, S. H., Basaraba, R. J., & Niederweis, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009261108 · Cited by 332 · see citing works
Copper Homeostasis at the Host-Pathogen Interface
Hodgkinson, V., & Petris, M. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.316406 · Cited by 316 · see citing works
Copper metallothionein of yeast, structure of the gene, and regulation of expression.
Butt, T. R., Sternberg, E. J., Gorman, J. A., et al. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.11.3332 · Cited by 285 · see citing works
Copper in Microbial Pathogenesis: Meddling with the Metal
Samanovic, M. I., Ding, C., Thiele, D. J., & Darwin, K. H. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.009 · Cited by 278 · see citing works
Self-citationYeast metallothionein. Sequence and metal-binding properties.
Winge, D. R., Nielson, K. B., Gray, W. R., et al. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38592-7 · Cited by 270 · see citing works
Chillappagari, S., Seubert, A., Trip, H., Kuipers, O. P., Marahiel, M. A., & Miethke, M. (2010) · Journal of Bacteriology · doi:10.1128/jb.00058-10 · Cited by 239 · see citing works
Novel gene functions required for melanization of the human pathogen Cryptococcus neoformans
Walton, F. J., Idnurm, A., & Heitman, J. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04779.x · Cited by 228 · see citing works
Self-citationCryptococcus: from human pathogen to model yeast.
Heitman, J., Kozel, T. R., Kwon-Chung, K. J., Perfect, J. R., & Casadevall, A. (2010) · Cited by 226 · see citing works
Self-citationJung, W. H., Sham, A. P., White, R., & Kronstad, J. W. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040410 · Cited by 222 · see citing works
Sustained Reduction of Microbial Burden on Common Hospital Surfaces through Introduction of Copper
Schmidt, M. G., Attaway, H. H., Sharpe, P. A., John, J. F., Sepkowitz, K. A., Morgan, A. B., Fairey, S. E., Singh, S., Steed, L. L., Cantey, J. R., et al. (2012) · Journal of Clinical Microbiology · doi:10.1128/jcm.01032-12 · Cited by 211 · see citing works
Characterization of the Saccharomyces cerevisiae High Affinity Copper Transporter Ctr3
Peña, M. M. O., Puig, S., & Thiele, D. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005392200 · Cited by 189 · see citing works
Self-citationBanerjee, D., Onosaka, S., & Cherian, M. G. (1982) · Toxicology · doi:10.1016/0300-483x(82)90048-8 · Cited by 184 · see citing works
Lay, J., Henry, L. K., Clifford, J., Koltin, Y., Bulawa, C. E., & Becker, J. M. (1998) · Infection and Immunity · doi:10.1128/iai.66.11.5301-5306.1998 · Cited by 174 · see citing works
Iron Source Preference and Regulation of Iron Uptake in Cryptococcus neoformans
Jung, W. H., Sham, A. P., Lian, T., Singh, A., Kosman, D. J., & Kronstad, J. W. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.0040045 · Cited by 158 · see citing works
Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity
Cassat, J. E., & Skaar, E. P. (2012) · Seminars in Immunopathology · doi:10.1007/s00281-011-0294-4 · Cited by 155 · 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
Pathogenicity of Candida albicans auxotrophic mutants in experimental infections
Kirsch, D. R., & Whitney, R. R. (1991) · Infection and Immunity · doi:10.1128/iai.59.9.3297-3300.1991 · Cited by 150 · see citing works
Bermingham‐McDonogh, O., Gralla, E. B., & Valentine, J. S. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.13.4789 · Cited by 148 · see citing works
Titan Cell Production Enhances the Virulence of Cryptococcus neoformans
Crabtree, J., Okagaki, L. H., Wiesner, D. L., Strain, A. K., Nielsen, J. N., & Nielsen, K. (2012) · Infection and Immunity · doi:10.1128/iai.00507-12 · Cited by 142 · see citing works
Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans
Waterman, S. R., Hacham, M., Hu, G., Zhu, X., Park, Y.-D., Shin, S., Panepinto, J., Valyi-Nagy, T., Beam, C., Husain, S., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30006 · Cited by 134 · see citing works
Nicola, A. M., Robertson, E. J., Albuquerque, P., Derengowski, L. D. S., & Casadevall, A. (2011) · mBio · doi:10.1128/mbio.00167-11 · Cited by 132 · see citing works
Resistance mechanisms of Mycobacterium tuberculosis against phagosomal copper overload
Rowland, J. L., & Niederweis, M. (2012) · Tuberculosis · doi:10.1016/j.tube.2011.12.006 · Cited by 131 · see citing works
Lin, X., Huang, J. C., Mitchell, T. G., & Heitman, J. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020187 · Cited by 126 · see citing works
Self-citationRole of Ferroxidases in Iron Uptake and Virulence of Cryptococcus neoformans
Jung, W. H., Hu, G., Kuo, W., & Kronstad, J. W. (2009) · Eukaryotic Cell · doi:10.1128/ec.00166-09 · Cited by 120 · see citing works
Cryptococcus: from human pathogen to model yeast
Boulware, D. R. (2011) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(11)70140-2 · Cited by 118 · see citing works
Kronstad, J., Saikia, S., Nielson, E. D., Kretschmer, M., Jung, W. H., Hu, G., Geddes, J. M. H., Griffiths, E., Choi, J., Cadieux, B., et al. (2011) · Eukaryotic Cell · doi:10.1128/ec.05273-11 · Cited by 116 · see citing works
Achard‐Joris, M., Tree, J. J., Holden, J. A., Simpfendorfer, K. R., Wijburg, O. L. C., Strugnell, R. A., Schembri, M. A., Sweet, M. J., Jennings, M. P., & McEwan, A. G. (2010) · Infection and Immunity · doi:10.1128/iai.01208-09 · Cited by 113 · see citing works
Commentary: The Role of Iron-Sulfur Clusters inin vivoHydroxyl Radical Production
Liochev, S. I. (1996) · Free Radical Research · doi:10.3109/10715769609149059 · Cited by 112 · see citing works
Durnam, D. M., & Palmiter, R. D. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.3.484 · Cited by 112 · see citing works
Zhou, H., & Thiele, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102004200 · Cited by 109 · see citing works
Self-citationThe copper regulon of the human fungal pathogenCryptococcus neoformansH99
Ding, C., Yin, J., Medina, E. M., Fitzpatrick, D. A., Higgins, D. G., & Thiele, D. J. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07794.x · Cited by 107 · see citing works
Self-citationIron and fungal pathogenesis: a case study with Cryptococcus neoformans
Jung, W. H., & Kronstad, J. W. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.01077.x · Cited by 105 · see citing works
A cysteine-rich nuclear protein activates yeast metallothionein gene transcription.
Szczypka, M. S., & Thiele, D. J. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.2.421 · Cited by 99 · see citing works
Self-citationURA3 as a selectable marker for disruption and virulence assessment of Candida albicans genes
Staab, J. F., & Sundstrom, P. (2003) · Trends in Microbiology · doi:10.1016/s0966-842x(02)00029-x · Cited by 96 · see citing works
Schwan, W. R., Warrener, P., Keunz, E., Kendall Stover, C., & Folger, K. R. (2005) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2005.05.005 · Cited by 86 · see citing works
Capdevila, M., Domènech-Casal, J., Pagani, M. A., et al. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200501183 · Cited by 82 · see citing works
Self-citationDing, C., & Butler, G. (2007) · Eukaryotic Cell · doi:10.1128/ec.00136-07 · Cited by 81 · see citing works
Self-citationBongers, J., Walton, C. D., Richardson, D. E., et al. (1988) · Analytical Chemistry · doi:10.1021/ac00175a008 · Cited by 80 · 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
Kwon-Chung, K. J., Varma, A., Edman, J. C., & Bennett, J. E. (1992) · Medical Mycology · doi:10.1080/02681219280000081 · Cited by 66 · see citing works
Ura-status-dependent adhesion of Candida albicans mutants
Bain, J. M., Stubberfield, C. R., & Gow, N. A. R. (2001) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2001.tb10905.x · Cited by 63 · see citing works
Role of CTR4 in the Virulence of Cryptococcus neoformans
Waterman, S. R., Park, Y., Raja, M., Qiu, J. F., Hammoud, D. A., O’Halloran, T. V., & Williamson, P. R. (2012) · mBio · doi:10.1128/mbio.00285-12 · Cited by 59 · see citing works
Ben‐Abdallah, M., Sturny-Leclère, A., Avé, P., Louise, A., Moyrand, F., Weih, F., Janbon, G., & Mémet, S. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002555 · Cited by 51 · see citing works
A Cysteine-Rich Nuclear Protein Activates Yeast Metallothionein Gene Transcription
Szczypka, M. S., & Thiele, D. J. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.2.421-429.1989 · Cited by 48 · see citing works
Self-citationBeaudoin, J., Laliberté, J., & Labbé, S. (2005) · Microbiology · doi:10.1099/mic.0.28392-0 · Cited by 44 · see citing works
Osman, D., & Cavet, J. S. (2011) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/b978-0-12-381043-4.00005-2 · Cited by 41 · see citing works
Kägi, J. H. R., & Hunziker, P. (1989) · Biological Trace Element Research · doi:10.1007/bf02917243 · Cited by 41 · see citing works
Analysis of the Detoxification of Heavy Metal Ions by Mouse Metallothionein
Durnam, D. M., & Palmiter, R. D. (1987) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0348-6784-9_45 · Cited by 40 · see citing works
Cryptococcus neoformans Is Resistant to Surfactant Protein A Mediated Host Defense Mechanisms
Giles, S. S., Zaas, A. K., Reidy, M. F., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001370 · Cited by 36 · see citing works
Durnam, D. M., & Palmiter, R. D. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.3.484-491.1984 · Cited by 32 · see citing works
Human defenses against Cryptococcus neoformans: An update
Brummer, E. (1998) · Mycopathologia · doi:10.1023/a:1006905331276 · Cited by 31 · see citing works
A Purified Capsular Polysaccharide Markedly Inhibits Inflammatory Response during Endotoxic Shock
Piccioni, M., Monari, C., Kenno, S., Pericolini, E., Gabrielli, E., Pietrella, D., Perito, S., Bistoni, F., Kozel, T. R., & Vecchiarelli, A. (2012) · Infection and Immunity · doi:10.1128/iai.00553-12 · Cited by 31 · see citing works
Pondugula, S., Neef, D. W., Voth, W. P., Darst, R. P., Dhasarathy, A., Reynolds, M., Takahata, S., Stillman, D. J., & Kladde, M. P. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00222-09 · Cited by 21 · see citing works
Formation of the metal-thiolate clusters of rat liver metallothionein.
Winge, D. R., & Nielson, K. B. (1984) · Environmental Health Perspectives · doi:10.1289/ehp.8454129 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis
Kwon-Chung, K. J., Fraser, J. A., Doering, T. L., Wang, Z. A., Janbon, G., Idnurm, A., & Bahn, Y.-S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019760 · Cited by 531 · 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
The Role of Copper Homeostasis at the Host-Pathogen Axis: From Bacteria to Fungi
Li, C., Li, Y., & Ding, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010175 · Cited by 107 · see citing works
Self-citationWiemann, P., Perevitsky, A., Lim, F. Y., Shadkchan, Y., Knox, B. P., Landero Figueora, J. A., Choera, T., Niu, M., Steinberger, A. J., Wüthrich, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.019 · Cited by 104 · see citing works
Sun, T.-S., Ju, X., Gao, H.-L., Wang, T., Thiele, D. J., Li, J.-Y., Wang, Z.-Y., & Ding, C. (2014) · Nature Communications · doi:10.1038/ncomms6550 · Cited by 94 · see citing works
Self-citationStress Signaling Pathways for the Pathogenicity of Cryptococcus
Bahn, Y.-S., & Jung, K.-W. (2013) · Eukaryotic Cell · doi:10.1128/ec.00218-13 · Cited by 84 · see citing works
Johnson, M. D. L., Kehl-Fie, T. E., Klein, R., Kelly, J., Burnham, C., Mann, B., & Rosch, J. W. (2015) · Infection and Immunity · doi:10.1128/iai.03015-14 · Cited by 84 · see citing works
Potrykus, J., Ballou, E. R., Childers, D. S., & Brown, A. J. P. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003910 · Cited by 52 · see citing works
Khemiri, I., Tebbji, F., & Sellam, A. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00935 · Cited by 40 · see citing works
Transcription factor Afmac1 controls copper import machinery in Aspergillus fumigatus
Kusuya, Y., Hagiwara, D., Sakai, K., Yaguchi, T., Gonoi, T., & Takahashi, H. (2017) · Current Genetics · doi:10.1007/s00294-017-0681-z · Cited by 34 · see citing works
Fu, C., Beattie, S. R., Jezewski, A. J., Robbins, N., Whitesell, L., Krysan, D. J., & Cowen, L. E. (2022) · Genetics · doi:10.1093/genetics/iyab164 · Cited by 31 · see citing works
Park, Y.-S., Kim, T.-H., & Yun, C.-W. (2017) · Biochemical Journal · doi:10.1042/bcj20170191 · Cited by 30 · see citing works
- Authors
- Ding, C., Festa, R. A., Chen, Y.-L., Espart, A., Palacios, Ò., Espín, J., Capdevila, M., Atrian, S., Heitman, J., & Thiele, D. J.
- Affiliations
- Duke University (US)
- Universitat de Barcelona (ES)
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Thiele, Dennis J.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 13
- Issue
- 3
- Pages
- 265-276
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3668348
- OpenAlex
- W2048443522
- Cited by
- 179
- References
- 70
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 15 · 2023: 15 · 2022: 13 · 2021: 14 · 2020: 13 · 2019: 17 · 2018: 11 · 2017: 27 · 2016: 12 · 2015: 11 · 2014: 14 · 2013: 8
- FWCI
- 10.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM041840, F32GM100678, GM48140-24)
- National Institute of Allergy and Infectious Diseases (AI-50438, R01AI050438, P30AI064518)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Cryptococcus neoformans, copper detoxification, metallothionein, fungal virulence, pulmonary infection, host innate immunity, copper homeostasis, ATP7A, alveolar macrophages, host-pathogen interaction
- MeSH terms
- Animals, Biological Transport, Bronchoalveolar Lavage Fluid, Copper, Cryptococcosis, Cryptococcus neoformans, Female, Fungal Proteins, Humans, Lung, Metallothionein, Virulence, Mice
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
