The DOI matches its Crossref record; 45 of the 47 references it cites were found in a registry or an index.
Carbonic Anhydrase and CO2 Sensing during Cryptococcus neoformans Growth, Differentiation, and Virulence
Open accessAbstract
The gas carbon dioxide (CO2) plays a critical role in microbial and mammalian respiration, photosynthesis in algae and plants, chemoreception in insects, and even global warming . However, how CO2 is transported, sensed, and metabolized by microorganisms is largely not understood. For instance, CO2 is known to induce production of polysaccharide capsule virulence determinants in pathogenic bacteria and fungi via unknown mechanisms . Therefore, we studied CO2 actions in growth, differentiation, and virulence of the basidiomycetous human fungal pathogen Cryptococcus neoformans. The CAN2 gene encoding beta-carbonic anhydrase in C. neoformans was found to be essential for growth in environmental ambient conditions but dispensable for in vivo proliferation and virulence at the high CO2 levels in the host. The can2Delta mutant in vitro growth defect is largely attributable to defective fatty acid synthesis. CO2 was found to inhibit cell-cell fusion but not filamentation during sexual reproduction. The can2 mutation restored early mating events in high CO2 but not later steps (fruiting body formation, sporulation), indicating a major role for carbonic anhydrase and CO2/HCO3- in this developmental cascade leading to the production of infectious spores. Our studies illustrate diverse roles of an ancient enzyme class in enabling environmental survival of a ubiquitous human pathogen.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Fungi sense CO2 by generating bicarbonate ions28–30 or directly through the type 2C-related protein phosphatase Ptc231, with a single orthologue B9J08_003504 in C. auris32.”
From Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103 (2025) · cites this paper as [29]
In the citing paper
“a CSP is well documented in other fungal species24,28,29,48,50”
From Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103 (2025) · cites this paper as [29]
Citations
Cites
Soluble Adenylyl Cyclase as an Evolutionarily Conserved Bicarbonate Sensor
Chen, Y., Cann, M. J., Litvin, T. N., Iourgenko, V., Sinclair, M. L., Levin, L. R., & Buck, J. (2000) · Science · doi:10.1126/science.289.5479.625 · Cited by 846
CO2 concentrating mechanisms in cyanobacteria: Molecular components, their diversity and evolution
Badger, M. R. (2003) · Journal of Experimental Botany · doi:10.1093/jxb/erg076 · Cited by 841
Fluorescence-Based Isolation of Bacterial Genes Expressed Within Host Cells
Valdivia, R. H., & Falkow, S. (1997) · Science · doi:10.1126/science.277.5334.2007 · Cited by 590
Carbonic Anhydrase: New Insights for an Ancient Enzyme
Tripp, B. C., Smith, K. S., & Ferry, J. G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r100045200 · Cited by 565
Suh, G. S. B., Wong, A. M., Hergarden, A. C., Wang, J. W., Simon, A. F., Benzer, S., Axel, R., & Anderson, D. J. (2004) · Nature · doi:10.1038/nature02980 · Cited by 563
Urease as a Virulence Factor in Experimental Cryptococcosis
Cox, G. M., Mukherjee, J., Cole, G. T., Casadevall, A., & Perfect, J. R. (2000) · Infection and Immunity · doi:10.1128/iai.68.2.443-448.2000 · Cited by 522
Self-citationFungal Adenylyl Cyclase Integrates CO2 Sensing with cAMP Signaling and Virulence
Klengel, T., Liang, W., Chaloupka, J., Ruoff, C., Schröppel, K., Naglik, J. R., Eckert, S. E., Mogensen, E. G., Haynes, K., Tuite, M. F., et al. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.040 · Cited by 409
Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMPPreprint
Alspaugh, J. A., Perfect, J. R., & Heitman, J. (1997) · Genes & Development · doi:10.1101/gad.11.23.3206 · Cited by 403
Self-citationDeciphering the Model Pathogenic Fungus Cryptococcus Neoformans
Idnurm, A., Bahn, Y., Nielsen, K., Lin, X., Fraser, J. A., & Heitman, J. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1245 · Cited by 347
Self-citationMultiple Roles of Carbonic Anhydrase in Cellular Transport and Metabolism
Henry, R. P. (1996) · Annual Review of Physiology · doi:10.1146/annurev.ph.58.030196.002515 · Cited by 323
Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide.
Granger, D. L., Perfect, J. R., & Durack, D. T. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112000 · Cited by 308
Self-citationA PCR-based strategy to generate integrative targeting alleles with large regions of homology
Davidson, R. C., Blankenship, J. R., Kraus, P. R., de Jesús-Berrı́os, M., Hull, C. M., D’Souza, C. A., Wang, P., & Heitman, J. (2002) · Microbiology · doi:10.1099/00221287-148-8-2607 · Cited by 296
Self-citationBahn, Y., Kojima, K., Cox, G. M., & Heitman, J. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-11-0987 · Cited by 274
Self-citationA Yeast under Cover: the Capsule ofCryptococcus neoformans
Bose, I., Reese, A. J., Ory, J. J., Janbon, G., & Doering, T. L. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.4.655-663.2003 · Cited by 231
Gene Disruption by Biolistic Transformation in Serotype D Strains of Cryptococcus neoformans
Davidson, R. C., Cruz, M. C., Sia, R. A. L., Allen, B., Alspaugh, J. A., & Heitman, J. (2000) · Fungal Genetics and Biology · doi:10.1006/fgbi.1999.1180 · Cited by 194
Self-citationKaryotyping of Cryptococcus neoformans as an epidemiological tool
Perfect, J. R., Ketabchi, N., Cox, G. M., Ingram, C. W., & Beiser, C. L. (1993) · Journal of Clinical Microbiology · doi:10.1128/jcm.31.12.3305-3309.1993 · Cited by 184
Self-citationThe alpha-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene.
Moore, T. D. E., & Edman, J. C. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.3.1962-1970.1993 · Cited by 178
Induction of Capsule Growth inCryptococcus neoformansby Mammalian Serum and CO2
Zaragoza, Ó., Fries, B. C., & Casadevall, A. (2003) · Infection and Immunity · doi:10.1128/iai.71.11.6155-6164.2003 · Cited by 175
Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain
Zippin, J. H., Farrell, J., Huron, D. R., Kamenetsky, M., Hess, K. C., Fischman, D. A., Levin, L. R., & Buck, J. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200311119 · Cited by 164
Navarro-Aviñó, J., Prasad, R., Miralles, V. J., Benito, R. M., & Serrano, R. (1999) · Yeast · doi:10.1002/(sici)1097-0061(199907)15:10a · Cited by 154
Carbonic anhydrase XII is a marker of good prognosis in invasive breast carcinoma
Watson, P. H., Chia, S., Wykoff, C. C., Han, C., Leek, R., Sly, W. S., Gatter, K. C., Ratcliffe, P. J., & Harris, A. L. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600796 · Cited by 152
Bahn, Y., Hicks, J. K., Giles, S. S., Cox, G. M., & Heitman, J. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.6.1476-1491.2004 · Cited by 121
Self-citationHull, C. M., Davidson, R. C., & Heitman, J. (2002) · Genes & Development · doi:10.1101/gad.1041402 · Cited by 119
Self-citationDavidson, R. C., Nichols, C. B., Cox, G. M., Perfect, J. R., & Heitman, J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03563.x · Cited by 119
Self-citationCarbonic Anhydrase Is Essential for Growth of Ralstonia eutropha at Ambient CO 2 Concentrations
Kusian, B., Sültemeyer, D. F., & Bowien, B. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.18.5018-5026.2002 · Cited by 115
CO2/HCO3−-responsive soluble adenylyl cyclase as a putative metabolic sensor
Zippin, J. H., Levin, L. R., & Buck, J. (2001) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00454-4 · Cited by 108
Signal Transduction Pathways Regulating Differentiation and Pathogenicity ofCryptococcus neoformans
Alspaugh, J. A., Perfect, J. R., & Heitman, J. (1998) · Fungal Genetics and Biology · doi:10.1006/fgbi.1998.1079 · Cited by 100
Self-citationHicks, J. K., D’Souza, C. A., Cox, G. M., & Heitman, J. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.1.14-26.2004 · Cited by 100
Self-citationStaab, J. F., & Sundstrom, P. (1998) · Yeast · doi:10.1002/(sici)1097-0061(199805)14:7 · Cited by 95
Cloning and CO2‐dependent expression of the genetic region for encapsulation from Bacillus anthracis
Makino, S., Sasakawa, C., Uchida, I., Terakado, N., & Yoshikawa, M. (1988) · Molecular Microbiology · doi:10.1111/j.1365-2958.1988.tb00041.x · Cited by 91
Aguilera, J., van Dijken, J. P., de Winde, J. H., & Pronk, J. T. (2005) · Biochemical Journal · doi:10.1042/bj20050556 · Cited by 88
Amoroso, G., Morell‐Avrahov, L., Müller, D., Klug, K., & Sültemeyer, D. F. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04560.x · Cited by 77
Mitsuhashi, S., Ohnishi, J., Hayashi, M., & Ikeda, M. (2004) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-003-1402-8 · Cited by 77
Kingsbury, J. M., Yang, Z., Ganous, T. M., Cox, G. M., & McCusker, J. H. (2004) · Microbiology · doi:10.1099/mic.0.26928-0 · Cited by 76
Self-citationMutation of the Regulator of G Protein Signaling Crg1 Increases Virulence in Cryptococcus neoformans
Wang, P., Cutler, J. E., King, J., & Palmer, D. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.4.1028-1035.2004 · Cited by 70
Capsule and melanin synthesis in Cryptococcus neoformans
McFadden, D. C., & Casadevall, A. (2001) · Medical Mycology · doi:10.1080/mmy.39.1.19.30 · Cited by 63
Role of bicarbonate/CO2 in the inhibition of Escherichia coli growth by cyanate
Kozliak, E. I., Fuchs, J. A., Guilloton, M., & Anderson, P. M. (1995) · Journal of Bacteriology · doi:10.1128/jb.177.11.3213-3219.1995 · Cited by 52
CLARK, D., Rowlett, R. S., Coleman, J. R., & Klessig, D. F. (2004) · Biochemical Journal · doi:10.1042/bj20031711 · Cited by 41
Acetyl-coenzyme A carboxylase from the developing endosperm of Ricinus communis
Finlayson, S. A., & Dennis, D. T. (1983) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(83)90069-3 · Cited by 39
Carbon Dioxide as a Growth Factor for Mutants of Escherichia coli
Charles, H. P., & Roberts, G. A. (1968) · Journal of General Microbiology · doi:10.1099/00221287-51-2-211 · Cited by 37
What Mosquitoes Want: Secrets of Host Attraction
Enserink, M. (2002) · Science · doi:10.1126/science.298.5591.90 · Cited by 32
Velocity of CO2 Exchanges in the Lungs
BIDANI, A. K., & Crandall, E. D. (1988) · Annual Review of Physiology · doi:10.1146/annurev.ph.50.030188.003231 · Cited by 31
Hetherington, A. M., & Raven, J. A. (2005) · Current Biology · doi:10.1016/j.cub.2005.05.042 · Cited by 28
Uno, I., Matsumoto, K., Hirata, A., & Ishikawa, T. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.100.6.1854 · Cited by 25
Phosphoenolpyruvate Carboxylase of Thiobacillus thioparus. I. General Properties
Hoban, D. J., & Lyric, R. M. (1975) · Canadian Journal of Biochemistry · doi:10.1139/o75-119 · Cited by 7
Research works printed but not linked: 1
- Hayashi, 1998, An extracellular meiosis-promoting factor in Saccharomyces cerevisiae, Yeast, 14, 617, 10.1002/(SICI)1097-0061(199805)14:7<617::AID-YEA265>3.0.CO;2-# · DOI
Cited by
Sorted by citations
Carbonic anhydrases: novel therapeutic applications for inhibitors and activators
Supuran, C. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2467 · Cited by 3,226
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
Self-citationBiswas, S., Dijck, P. V., & Datta, A. (2007) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00009-06 · Cited by 539
Sensing the environment: lessons from fungi
Bahn, Y., Xue, C., Idnurm, A., Rutherford, J. C., Heitman, J., & Cardenas, M. E. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1578 · Cited by 416
Self-citationFungal Adenylyl Cyclase Integrates CO2 Sensing with cAMP Signaling and Virulence
Klengel, T., Liang, W., Chaloupka, J., Ruoff, C., Schröppel, K., Naglik, J. R., Eckert, S. E., Mogensen, E. G., Haynes, K., Tuite, M. F., et al. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.040 · Cited by 409
Metadata
- Authors
- Bahn, Y.-S., Cox, G. M., Perfect, J. R., & Heitman, J.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Heitman, Joseph
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 15
- Issue
- 22
- Pages
- 2013-2020
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W1968110247
- Cited by
- 205
- References
- 47
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 4 · 2019: 9 · 2018: 8 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 18 · 2013: 14 · 2012: 9
- FWCI
- 10.04
- 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, 2815 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
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI39115, AI44975, AI50113)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- carbonic anhydrase, carbon dioxide detection, Cryptococcus neoformans, beta-carbonic anhydrase, fungal virulence, fatty acid synthesis, cell-cell fusion, sexual differentiation, mating, fruiting body formation, sporulation, human fungal pathogens, environmental survival
- MeSH terms
- Base Sequence, Bicarbonates, Carbon Dioxide, Carbonic Anhydrases, Cell Adhesion, Cryptococcus neoformans, DNA Mutational Analysis, Fatty Acids, Molecular Sequence Data, Mutation, Reproduction, Spores, Fungal, Blotting, Northern, Sequence Analysis, DNA, Computational Biology
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