The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity
Open accessAbstract
Candida albicans is the most common cause of serious fungal disease in humans. Creation of isogenic null mutants of this diploid organism, which requires sequential gene targeting, allows dissection of virulence mechanisms. Published analyses of such mutants show a near-perfect correlation between C. albicans pathogenicity and the ability to undergo a yeast-to-hypha morphological switch in vitro. However, most studies have used mutants constructed with a marker that is itself a virulence determinant and therefore complicates their interpretation. Using alternative markers, we created approximately 3,000 homozygous deletion strains affecting 674 genes, or roughly 11% of the C. albicans genome. Screening for infectivity in a mouse model and for morphological switching and cell proliferation in vitro, we identified 115 infectivity-attenuated mutants, of which nearly half demonstrated normal morphological switching and proliferation. Analysis of such mutants revealed that virulence requires the glycolipid glucosylceramide. To our knowledge, this is the first C. albicans small molecule that has been found to be required specifically for virulence.
Overview
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
Verification
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It has been reported that among 674 C. albicans gene-deleted mutants, 59% of these growth-defective mutants were competent for virulence, and 79% of virulence-defective mutants showed a normal growth in vitro, indicating that growth defects were not necessarily correlated to virulence31.”
From The δ subunit of F1Fo-ATP synthase is required for pathogenicity of Candida albicans (2021) · cites this paper as [31]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The growth ability30–32 and virulence factor production31 of C. albicans in the host determine the infection trend, and the former affects the latter to some extent, but the latter is not always affected by the former31.”
From The δ subunit of F1Fo-ATP synthase is required for pathogenicity of Candida albicans (2021) · cites this paper as [31]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It has been reported that among 674 C. albicans gene-deleted mutants, 59% of these growth-defective mutants were competent for virulence, and 79% of virulence-defective mutants showed a normal growth in vitro, indicating that growth defects were not necessarily correlated to virulence31.”
From The δ subunit of F1Fo-ATP synthase is required for pathogenicity of Candida albicans (2021) · cites this paper as [31]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Importantly, of these complex proteins, orf19.287 and orf19.6607 are fungus specific, and both deleted mutants are attenuated or avirulent (24).”
From Azole Susceptibility and Transcriptome Profiling in Candida albicans Mitochondrial Electron Transport Chain Complex I Mutants (2013) · cites this paper as [24]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Importantly, of these complex proteins, orf19.287 and orf19.6607 are fungus specific, and both deleted mutants are attenuated or avirulent (24).”
From Azole Susceptibility and Transcriptome Profiling in Candida albicans Mitochondrial Electron Transport Chain Complex I Mutants (2013) · cites this paper as [24]
Experimental — accuracy not yet measured
In the citing paper
“This is consistent with the observations of Noble and co-workers that in vitro fitness is not always a reflection of virulence (Noble et al., 2010).”
From The evolution of drug resistance in clinical isolates of Candida albicans. (2015) · cites this paper as Noble et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Nosocomial Bloodstream Infections in United States Hospitals: A Three‐Year Analysis
Edmond, M. B., Wallace, S. E., McClish, D. K., Pfaller, M. A., Jones, R. N., & Wenzel, R. P. (1999) · Clinical Infectious Diseases · doi:10.1086/520192 · Cited by 1,387
Quorum Sensing in the Dimorphic Fungus Candida albicans Is Mediated by Farnesol
Hornby, J. M., Jensen, E. C., Lisec, A. D., Tasto, J. J., Jahnke, B., Shoemaker, R., Dussault, P., & Nickerson, K. W. (2001) · Applied and Environmental Microbiology · doi:10.1128/aem.67.7.2982-2992.2001 · Cited by 983
The distinct morphogenic states of Candida albicans
Sudbery, P., Gow, N., & Berman, J. (2004) · Trends in Microbiology · doi:10.1016/j.tim.2004.05.008 · Cited by 876
The diploid genome sequence of Candida albicans
Jones, T., Federspiel, N. A., Chibana, H., Dungan, J. M., Kalman, S., Magee, B. B., Newport, G., Thorstenson, Y. R., Agabian, N. M., Magee, P. T., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401648101 · Cited by 784
Zaoutis, T. E., Argon, J., Chu, J., Berlin, J. A., Walsh, T. J., & Feudtner, C. (2005) · Clinical Infectious Diseases · doi:10.1086/496922 · Cited by 784
Noble, S. M., & Johnson, A. D. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.2.298-309.2005 · Cited by 592
Self-citationRecombination-mediated PCR-directed plasmid construction in vivo in yeast
Oldenburg, K. R. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.2.451 · Cited by 516
Roemer, T., Jiang, B., Davison, J., Ketela, T. W., Veillette, K., Breton, A., Tandia, F., Linteau, A., Sillaots, S., Marta, C., et al. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03697.x · Cited by 513
Morphogenesis in Candida albicans
Whiteway, M. S., & Bachewich, C. (2007) · Annual Review of Microbiology · doi:10.1146/annurev.micro.61.080706.093341 · Cited by 408
Rocha, C. R. C., Schröppel, K., Harcus, D., Marcil, A., Dignard, D., Taylor, B. N., Thomas, D. Y., Whiteway, M. S., & Leberer, E. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.11.3631 · Cited by 349
Kadosh, D., & Johnson, A. D. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0073 · Cited by 295
Self-citationBrand, A., MacCallum, D. M., Brown, A. J. P., Gow, N. A. R., & Odds, F. C. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.4.900-909.2004 · Cited by 277
Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans
Rittershaus, P. C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27890 · Cited by 239
The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence in Candida albicans
Cao, F., Lane, S., Raniga, P. P., Lü, Y., Zhou, Z., Ramon, K., Chen, J., & Liu, H. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-06-0502 · Cited by 215
Uhl, M. A., Biery, M., Craig, N., & Johnson, A. D. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg256 · Cited by 191
Self-citationThe Candida albicans CaACE2 gene affects morphogenesis, adherence and virulence
Kelly, M. T., MacCallum, D. M., Clancy, S. D., Odds, F. C., Brown, A. J. P., & Butler, G. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04185.x · Cited by 175
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
Leipelt, M., Warnecke, D. C., Zähringer, U., Ott, C., Müller, F., Hube, B., & Heinz, E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104952200 · Cited by 171
MacCallum, D., & Odds, F. (2005) · Mycoses (Berlin) · doi:10.1111/j.1439-0507.2005.01121.x · Cited by 159
Selmecki, A., Bergmann, S., & Berman, J. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04492.x · Cited by 157
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 147
Enjalbert, B., & Whiteway, M. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.7.1203-1210.2005 · Cited by 145
Zaragoza, Ó., Blázquez, M. A., & Gancedo, C. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.15.3809-3815.1998 · Cited by 141
Sundstrom, P., Cutler, J., & Staab, J. (2002) · Infection and Immunity · doi:10.1128/iai.70.6.3281-3283.2002 · Cited by 128
Miwa, T., Takagi, Y., Shinozaki, M., Yun, C., Schell, W. A., Perfect, J. R., Kumagai, H., & Tamaki, H. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.4.919-931.2004 · Cited by 125
Inhibition of Filamentation Can Be Used To Treat Disseminated Candidiasis
Saville, S. P., Lazzell, A. L., Bryant, A. P., Fretzen, A., Monreal, A., Solberg, E. O., Monteagudo, C. C., Lopez-Ribot, J. L., & Milne, G. T. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00628-06 · Cited by 115
Heterozygosity of genes on the sex chromosome regulates Candida albicans virulence
Wu, W., Lockhart, S. R., Pujol, C., Srikantha, T., & Soll, D. R. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05759.x · Cited by 104
Candida albicans Septin Mutants Are Defective for Invasive Growth and Virulence
Warenda, A. J., Kauffman, S., Sherrill, T. P., Becker, J. M., & Konopka, J. B. (2003) · Infection and Immunity · doi:10.1128/iai.71.7.4045-4051.2003 · Cited by 99
Cheng, S., Nguyen, M. H., Zhang, Z., Jia, H., Handfield, M., & Clancy, C. J. (2003) · Infection and Immunity · doi:10.1128/iai.71.10.6101-6103.2003 · Cited by 91
Aneuploid Chromosomes Are Highly Unstable during DNA Transformation of Candida albicans
Bouchonville, K. J., Forche, A., Tang, K. E. S., Selmecki, A. M., & Berman, J. G. (2009) · Eukaryotic Cell · doi:10.1128/ec.00209-09 · Cited by 89
Chromosome 1 trisomy compromises the virulence of Candida albicans
Chen, X., Magee, B. B., Dawson, D., Magee, P. T., & Kumamoto, C. A. (2004) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03852.x · Cited by 86
Use of signature-tagged mutagenesis in pathogenesis studies
Mecsas, J. C. (2002) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(02)00282-5 · Cited by 83
Signature-tagged mutagenesis in the identification of virulence genes in pathogens
Shea, J. E., Santangelo, J. D., & Feldman, R. G. (2000) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(00)00120-x · Cited by 77
Saenz, H., & Dehio, C. (2005) · Current Opinion in Microbiology · doi:10.1016/j.mib.2005.08.013 · Cited by 77
An RNA Transport System in Candida albicans Regulates Hyphal Morphology and Invasive Growth
Elson, S. L., Noble, S. M., Solis, N. V., Filler, S. G., & Johnson, A. D. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000664 · Cited by 76
Self-citationCandida albicans sphingolipid C9-methyltransferase is involved in hyphal elongation
Oura, T., & Kajiwara, S. (2009) · Microbiology · doi:10.1099/mic.0.033985-0 · Cited by 71
New tools at the Candida Genome Database: biochemical pathways and full-text literature search
Skrzypek, M. S., Arnaud, M. B., Costanzo, M. C., Inglis, D. O., Shah, P., Binkley, G., Miyasato, S. R., & Sherlock, G. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp836 · Cited by 67
Mitrovich, Q. M., Tuch, B. B., Guthrie, C., & Johnson, A. D. (2007) · Genome Research · doi:10.1101/gr.6111907 · Cited by 66
Self-citationJia, N., Arthington-Skaggs, B., Lee, W., Pierson, C. A., Lees, N. D., Eckstein, J., Barbuch, R., & Bard, M. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.4.947-957.2002 · Cited by 61
Trimorphic stepping stones pave the way to fungal virulence
Bastidas, R. J., & Heitman, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811994106 · Cited by 61
Oura, T., & Kajiwara, S. (2008) · Microbiology · doi:10.1099/mic.0.2008/018788-0 · Cited by 58
Pedreño, Y., Párraga, P. G., Martinez‐Esparza, M., Sentandreu, R., Valentı́n, E., & Argüelles, J. C. (2007) · Microbiology · doi:10.1099/mic.0.2006/003921-0 · Cited by 58
Arbour, M., Epp, E., Hogues, H., Sellam, A., Lacroix, C., Rauceo, J. M., Mitchell, A. P., Whiteway, M. S., & Nantel, A. (2009) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2009.00563.x · Cited by 57
Mio, T., Kokado, M., Arisawa, M., & Yamada‐Okabe, H. (2000) · Microbiology · doi:10.1099/00221287-146-7-1753 · Cited by 47
Deficiency of d -Erythroascorbic Acid Attenuates Hyphal Growth and Virulence of Candida albicans
Huh, W., Kim, S., Kim, H., Jeong, G., & Kang, S.-O. (2001) · Infection and Immunity · doi:10.1128/iai.69.6.3939-3946.2001 · Cited by 45
Flanking direct repeats of hisG alter URA3 marker expression at the HWP1 locus of Candida albicans
Sharkey, L. L., Liao, W.-L., Ghosh, A. K., & Fonzi, W. A. (2005) · Microbiology · doi:10.1099/mic.0.27487-0 · Cited by 43
Donovan, M. G., Schumuke, J. J., Fonzi, W. A., Bonar, S. L., Mullis, K. G., Jacob, G. S., Davisson, V. J., & Dotson, S. B. (2001) · Infection and Immunity · doi:10.1128/iai.69.4.2542-2548.2001 · Cited by 37
Unanticipated Heterogeneity in Growth Rate and Virulence among Candida albicans AAF1 Null Mutants
Rieg, G., Fu, Y., Ibrahim, A. S., Zhou, X., Filler, S. G., & Edwards, J. E. (1999) · Infection and Immunity · doi:10.1128/iai.67.7.3193-3198.1999 · Cited by 36
Badrane, H., Nguyen, M. H., Cheng, S., Kumar, V., Derendorf, H., Iczkowski, K. A., & Clancy, C. J. (2008) · Microbiology · doi:10.1099/mic.0.2008/018002-0 · Cited by 27
Argüelles, J. C., Rodriguez, T., & Alvarez-Peral, F. J. (1999) · Research in Microbiology · doi:10.1016/s0923-2508(99)00105-9 · Cited by 18
Research works printed but not linked: 1
- Ausubel, F.M. et al. (eds.) Current Protocols in Molecular Biology (John Wiley & Sons, New York, 1990).
Cited by
Sorted by citations
Growth of Candida albicans hyphae
Sudbery, P. E. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2636 · Cited by 1,110
Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801
Phenotypic Landscape of a Bacterial Cell
Nichols, R. J., Sen, Ś., Choo, Y. J., Beltrão, P., Zietek, M., Chaba, R., Lee, S., Kazmierczak, K. M., Lee, K. J., Wong, A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.11.052 · Cited by 723
A Recently Evolved Transcriptional Network Controls Biofilm Development in Candida albicans
Nobile, C. J., Fox, E. P., Nett, J. E., Sorrells, T. R., Mitrovich, Q. M., Hernday, A. D., Tuch, B. B., Andes, D. R., & Johnson, A. D. (2012) · Cell · doi:10.1016/j.cell.2011.10.048 · Cited by 711
Self-citationRegulatory circuitry governing fungal development, drug resistance, and disease.
Shapiro, R. S., Robbins, N., & Cowen, L. E. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00045-10 · Cited by 576
Metadata
- Authors
- Noble, S. M., French, S., Kohn, L. A., Chen, V., & Johnson, A. D.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Noble, Suzanne M
- Venue
- Nature Genetics
- Published
- 2010-06-13
- Volume
- 42
- Issue
- 7
- Pages
- 590-598
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2893244
- OpenAlex
- W2139307267
- Cited by
- 678
- References
- 50
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 31 · 2023: 31 · 2022: 35 · 2021: 53 · 2020: 46 · 2019: 51 · 2018: 45 · 2017: 51 · 2016: 51 · 2015: 50 · 2014: 42 · 2013: 51 · 2012: 45
- FWCI
- 19.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Public Health Service (R01 A149187)
- National Institute of Allergy and Infectious Diseases (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 › Infectious Diseases › Fungal Infections and Studies
- Keywords
- Candida albicans, virulence, infectivity, mouse infection model, glucosylceramide, glycolipids, cell proliferation, fungal pathogenicity
- MeSH terms
- Animals, Candida albicans, Candidiasis, Female, Fungal Proteins, Glucosylceramides, Homozygote, Humans, Mice, Inbred BALB C, Morphogenesis, Mutation, Virulence, Molecular Structure, Gene Library, Survival Analysis, Gene Deletion, Hyphae, 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
