Carbonic Anhydrase and CO2 Sensing during Cryptococcus neoformans Growth, Differentiation, and Virulence
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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.
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Fungi sense CO2 by generating bicarbonate ions or directly through the type 2C-related protein phosphatase Ptc2, with a single orthologue B9J08_003504 in C. auris.
“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]
A CSP is well documented in other fungal species.
“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]
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 337 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationInduction 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 · see citing works
The α-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 170 · see citing works
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 · see citing works
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 147 · see citing works
Götz, R., Gnann, A., & Zimmermann, F. K. (1999) · Yeast · doi:10.1002/(sici)1097-0061(199907)15:10a · Cited by 124 · see citing works
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 · see citing works
Self-citationHull, C. M., Davidson, R. C., & Heitman, J. (2002) · Genes & Development · doi:10.1101/gad.1041402 · Cited by 119 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationCloning 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 · see citing works
Aguilera, J., van Dijken, J. P., de Winde, J. H., & Pronk, J. T. (2005) · Biochemical Journal · doi:10.1042/bj20050556 · Cited by 88 · see citing works
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 · see citing works
Mitsuhashi, S., Ohnishi, J., Hayashi, M., & Ikeda, M. (2004) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-003-1402-8 · Cited by 77 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Ohkuni, K., Hayashi, M., & Yamashita, I. (1998) · Yeast · doi:10.1002/(sici)1097-0061(199805)14:7 · Cited by 57 · see citing works
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 · see citing works
CLARK, D., Rowlett, R. S., Coleman, J. R., & Klessig, D. F. (2004) · Biochemical Journal · doi:10.1042/bj20031711 · Cited by 41 · see citing works
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 · see citing works
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 · see citing works
What Mosquitoes Want: Secrets of Host Attraction
Enserink, M. (2002) · Science · doi:10.1126/science.298.5591.90 · Cited by 32 · see citing works
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 · see citing works
Hetherington, A. M., & Raven, J. A. (2005) · Current Biology · doi:10.1016/j.cub.2005.05.042 · Cited by 28 · see citing works
Uno, I., Matsumoto, K., Hirata, A., & Ishikawa, T. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.100.6.1854 · Cited by 25 · see citing works
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 · see citing works
Flagged first, then by citations
2 of the 47 references couldn’t be matched to a known paper.
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 · see citing works
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
Self-citationBiswas, S., Dijck, P. V., & Datta, A. (2007) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00009-06 · Cited by 516 · see citing works
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 · see citing works
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 · see citing works
The Biology of theCryptococcus neoformansSpecies Complex
Lin, X., & Heitman, J. (2006) · Annual Review of Microbiology · doi:10.1146/annurev.micro.60.080805.142102 · Cited by 398 · see citing works
Self-citationThe Cryptococcus neoformans Capsule: a Sword and a Shield
O’Meara, T. R., & Alspaugh, J. A. (2012) · Clinical Microbiology Reviews · doi:10.1128/cmr.00001-12 · Cited by 365 · see citing works
The myriad roles of cyclic AMP in microbial pathogens: from signal to sword
McDonough, K. A., & Rodrı́guez, A. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2688 · Cited by 330 · see citing works
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 · see citing works
Quorum sensing: A less known mode of communication among fungi
Padder, S. A., Prasad, R., & Shah, A. H. (2018) · Microbiological Research · doi:10.1016/j.micres.2018.03.007 · Cited by 216 · see citing works
Schlicker, C., Hall, R. A., Vullo, D., Middelhaufe, S., Gertz, M., Supuran, C. T., Mühlschlegel, F. A., & Steegborn, C. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.11.037 · Cited by 200 · see citing works
CO2 Regulates White-to-Opaque Switching in Candida albicans
Huang, G., Srikantha, T., Sahni, N., Song, Y., & Soll, D. R. (2009) · Current Biology · doi:10.1016/j.cub.2009.01.018 · Cited by 180 · see citing works
Carbonic anhydrase inhibitors and activators and their use in therapy
Scozzafava, A., Mastrolorenzo, A., & Supuran, C. T. (2006) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.16.12.1627 · Cited by 178 · see citing works
Belden, W. J., Larrondo, L. F., Froehlich, A. C., Shi, M., Chen, C., Loros, J., & Dunlap, J. (2007) · Genes & Development · doi:10.1101/gad.1551707 · Cited by 173 · see citing works
Nishimori, I., Minakuchi, T., Kohsaki, T., Onishi, S., Takeuchi, H., Vullo, D., Scozzafava, A., & Supuran, C. T. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.04.063 · Cited by 168 · see citing works
Mogensen, E. G., Janbon, G., Chaloupka, J., Steegborn, C., Fu, M. S., Moyrand, F., Klengel, T., Pearson, D., Geeves, M. A., Buck, J., et al. (2006) · Eukaryotic Cell · doi:10.1128/ec.5.1.103-111.2006 · Cited by 168 · see citing works
Cryptococcus neoformans: Morphogenesis, infection, and evolution
Lin, X. (2009) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2009.01.013 · Cited by 166 · see citing works
CO2 sensing in fungi and beyond
Bahn, Y., & Mühlschlegel, F. A. (2006) · Current Opinion in Microbiology · doi:10.1016/j.mib.2006.09.003 · Cited by 160 · see citing works
Self-citationSignalling pathways in the pathogenesis of Cryptococcus
Kozubowski, L., Lee, S. C., & Heitman, J. (2008) · Cellular Microbiology · doi:10.1111/j.1462-5822.2008.01273.x · Cited by 150 · see citing works
Self-citationRamanan, R., Krishnamurthi, K., Sivanesan, S. D., Mudliar, S. N., Kaur, S., Tripathi, A. K., & Chakrabarti, T. (2009) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-009-9975-8 · Cited by 144 · see citing works
Virulence-Associated Enzymes of Cryptococcus neoformans
Almeida, F., Wolf, J. M., & Casadevall, A. (2015) · Eukaryotic Cell · doi:10.1128/ec.00103-15 · Cited by 141 · see citing works
Molecular mechanisms of cryptococcal meningitis
Liu, T.-B., Perlin, D. S., & Xue, C. (2012) · Virulence · doi:10.4161/viru.18685 · Cited by 131 · see citing works
Blieck, L., Toye, G., Dumortier, F. M., Verstrepen, K. J., Delvaux, F. R., Thevelein, J. M., & Dijck, P. V. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.02109-06 · Cited by 130 · see citing works
CO2 Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans
Hall, R. A., De Sordi, L., MacCallum, D. M., Topal, H., Eaton, R., Bloor, J. W., Robinson, G. K., Levin, L. R., Buck, J., Wang, Y., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001193 · Cited by 126 · see citing works
Carbon dioxide-sensing in organisms and its implications for human disease
Cummins, E. P., Selfridge, A. C., Sporn, P. H. S., Sznajder, J. I., & Taylor, C. T. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1470-6 · Cited by 127 · see citing works
Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals
Trevijano-Contador, N., de Oliveira, H. C., García-Rodas, R., Rossi, S. A., Llorente, I., Zaballos, Á., Janbon, G., Ariño, J., & Zaragoza, Ó. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007007 · Cited by 124 · see citing works
Elleuche, S., & Pöggeler, S. (2009) · Microbiology · doi:10.1099/mic.0.032581-0 · Cited by 124 · see citing works
The Impacts of Environmental Pollutants on Microalgae and Cyanobacteria
Ramakrishnan, B., Megharaj, M., Venkateswarlu, K., Naidu, R., & Sethunathan, N. (2010) · Critical Reviews in Environmental Science and Technology · doi:10.1080/10643380802471068 · Cited by 116 · see citing works
Borrelia burgdorferi Alters Its Gene Expression and Antigenic Profile in Response to CO 2 Levels
Hyde, J. A., Trzeciakowski, J. P., & Skare, J. T. (2006) · Journal of Bacteriology · doi:10.1128/jb.01109-06 · Cited by 103 · see citing works
Monti, S. M., Maresca, A., Viparelli, F., Carta, F., Simone, G. D., Mühlschlegel, F. A., Scozzafava, A., & Supuran, C. T. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.12.033 · Cited by 102 · see citing works
Natural Product-Based Phenols as Novel Probes for Mycobacterial and Fungal Carbonic Anhydrases
Davis, R. A., Hofmann, A., Osman, A., Hall, R. A., Mühlschlegel, F. A., Vullo, D., Innocenti, A., Supuran, C. T., & Poulsen, S. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm1013242 · Cited by 102 · see citing works
Innocenti, A., Mühlschlegel, F. A., Hall, R. A., Steegborn, C., Scozzafava, A., & Supuran, C. T. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.122 · Cited by 100 · see citing works
Profiling a killer, the development of Cryptococcus neoformans
Kozubowski, L., & Heitman, J. (2011) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2011.00286.x · Cited by 97 · see citing works
Self-citationSyrjänen, L., Vermelho, A. B., Rodrigues, I. A., Côrte‐Real, S., Salonen, T., Pan, P., Vullo, D., Parkkila, S., Capasso, C., & Supuran, C. T. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400939k · Cited by 94 · see citing works
Işık, S., KOCKAR, F. T., Aydın, M., Arslan, O., Güler, Ö. Ö., Innocenti, A., Scozzafava, A., & Supuran, C. T. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.12.035 · Cited by 91 · see citing works
Lipid signalling in pathogenic fungi
Singh, A., & Poeta, M. D. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01550.x · Cited by 88 · see citing works
Costa, M., Borges, C. L., Bailão, A. M., Meirelles, G. V., Mendonça, Y. A., Dantas, S. F. I. M., de Faria, F. P., Felipe, M. S. S., Molinari-Madlum, E. E. W. I., Mendes‐Giannini, M. J. S., et al. (2007) · Microbiology · doi:10.1099/mic.0.2007/009332-0 · Cited by 85 · see citing works
Syrjänen, L., Tolvanen, M. E. E., Hilvo, M., Olatubosun, A., Innocenti, A., Scozzafava, A., Leppiniemi, J., Taskinen, B., Hytönen, V. P., Gorr, T. A., et al. (2010) · BMC Biochemistry · doi:10.1186/1471-2091-11-28 · Cited by 84 · see citing works
Singh, A., Wang, H., Silva, L. C., Na, C., Prieto, M., Futerman, A. H., Luberto, C., & Del Poeta, M. (2012) · Cellular Microbiology · doi:10.1111/j.1462-5822.2011.01735.x · Cited by 81 · see citing works
Innocenti, A., Hall, R. A., Schlicker, C., Mühlschlegel, F. A., & Supuran, C. T. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.02.058 · Cited by 72 · see citing works
Carbonic anhydrase versatility: from pH regulation to CO2 sensing and metabolism
Supuran, C. T. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1326633 · Cited by 71 · see citing works
Fungal adaptation to the mammalian host: it is a new world, after all
Cooney, N. M., & Klein, B. S. (2008) · Current Opinion in Microbiology · doi:10.1016/j.mib.2008.09.018 · Cited by 68 · see citing works
Evolution of carbonic anhydrases in fungi
Elleuche, S., & Pöggeler, S. (2009) · Current Genetics · doi:10.1007/s00294-009-0238-x · Cited by 68 · see citing works
Sexual Reproduction of Human Fungal PathogensPreprint
Heitman, J., Carter, D. A., Dyer, P. S., & Soll, D. R. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019281 · Cited by 66 · see citing works
Self-citationCarbonic Anhydrase Is Essential forStreptococcus pneumoniaeGrowth in Environmental Ambient Air
Burghout, P., Cron, L. E., Gradstedt, H., Quintero, B., Simonetti, E. R., Bijlsma, J. J. E., Bootsma, H. J., & Hermans, P. W. M. (2010) · Journal of Bacteriology · doi:10.1128/jb.00151-10 · Cited by 65 · see citing works
The filamentous fungus Sordaria macrospora as a genetic model to study fruiting body development.
Teichert, I., Nowrousian, M., Pöggeler, S., & Kück, U. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00004-4 · Cited by 64 · see citing works
Eastwood, D. C., Herman, B., Noble, R., Dobrovin‐Pennington, A., Sreenivasaprasad, S., & Burton, K. S. (2013) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2013.01.001 · Cited by 63 · see citing works
The cAMP/Protein Kinase A Pathway and Virulence in Cryptococcus neoformans
Kronstad, J. W., Hu, G., & Choi, J.-H. (2011) · Mycobiology · doi:10.5941/myco.2011.39.3.143 · Cited by 63 · see citing works
Climate change, aerobiology, and public health in the Northeast United States
Ziska, L. H., Epstein, P. R., & Rogers, C. A. (2007) · Mitigation and Adaptation Strategies for Global Change · doi:10.1007/s11027-007-9134-1 · Cited by 62 · see citing works
Cottier, F., & Mühlschlegel, F. (2011) · International Journal of Microbiology · doi:10.1155/2012/351832 · Cited by 59 · see citing works
Proteome map of Aspergillus nidulans during osmoadaptation
Kim, Y., Nandakumar, M. P., & Marten, M. R. (2007) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2006.12.001 · Cited by 59 · see citing works
Fan, W., Idnurm, A., Breger, J., Mylonakis, E., & Heitman, J. (2007) · Infection and Immunity · doi:10.1128/iai.01977-06 · Cited by 57 · see citing works
Self-citationInnocenti, A., Hall, R. A., Schlicker, C., Scozzafava, A., Steegborn, C., Mühlschlegel, F. A., & Supuran, C. T. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.05.002 · Cited by 57 · see citing works
Sensing, physiological effects and molecular response to elevated CO 2 levels in eukaryotes
Sharabi, K., Lecuona, E., Helenius, I. T., Beitel, G. J., Sznajder, J. I., & Gruenbaum, Y. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00952.x · Cited by 56 · see citing works
The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast
Cottier, F., Raymond, M., Kurzai, O., Bolstad, M., Leewattanapasuk, W., Jiménez-López, C., Lorenz, M. C., Sanglard, D., Váchová, L., Pavelka, N., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002485 · Cited by 55 · see citing works
The transcription factor Flo8 mediates CO2sensing in the human fungal pathogenCandida albicans
Du, H., Guan, G., Xie, J., Cottier, F., Sun, Y., Jia, W., Mühlschlegel, F. A., & Huang, G. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-02-0094 · Cited by 55 · see citing works
Innocenti, A., Winum, J., Hall, R. A., Mühlschlegel, F. A., Scozzafava, A., & Supuran, C. T. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.03.147 · Cited by 54 · see citing works
Protein kinase A and fungal virulence
Fuller, K. K., & Rhodes, J. C. (2012) · Virulence · doi:10.4161/viru.19396 · Cited by 53 · see citing works
The intrinsically disordered region from PP2C phosphatases functions as a conserved CO2 sensor
Zhang, M., Zhu, C., Duan, Y., Liu, T., Liu, H., Su, C., & Lü, Y. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00936-6 · Cited by 53 · see citing works
Price, M. S., Nichols, C. B., & Alspaugh, J. A. (2008) · Infection and Immunity · doi:10.1128/iai.00896-08 · Cited by 49 · see citing works
Nishimori, I., Vullo, D., Minakuchi, T., Scozzafava, A., Osman, S. M., ALOthman, Z. A., Capasso, C., & Supuran, C. T. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.12.124 · Cited by 50 · see citing works
Işık, S., KOCKAR, F. T., Arslan, O., Güler, Ö. Ö., Innocenti, A., & Supuran, C. T. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.10.100 · Cited by 49 · see citing works
The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans
Xue, C., Hsueh, Y., Chen, L., & Heitman, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06417.x · Cited by 49 · see citing works
Self-citationSupuran, C. T., & Capasso, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094324 · Cited by 49 · see citing works
Kim, M. S., Ko, Y.-J., Maeng, S., Floyd, A., Heitman, J., & Bahn, Y.-S. (2010) · Genetics · doi:10.1534/genetics.110.118315 · Cited by 48 · see citing works
Self-citationUnisexual versus bisexual mating in Cryptococcus neoformans: Consequences and biological impacts
Fu, C., Sun, S., Billmyre, R. B., Roach, K. C., & Heitman, J. (2014) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2014.08.008 · Cited by 48 · see citing works
Self-citationXiao, L., Hao, J., Wang, W., Lian, B., Shang, G., Yang, Y., Liu, C., & Wang, S. (2014) · Geomicrobiology Journal · doi:10.1080/01490451.2014.884195 · Cited by 47 · see citing works
Plant-biotic interactions under elevated CO2: A molecular perspective
Kazan, K. (2018) · Environmental and Experimental Botany · doi:10.1016/j.envexpbot.2018.06.005 · Cited by 47 · see citing works
Paul, S., Bair, T. B., & Moye-Rowley, W. S. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03921-14 · Cited by 45 · see citing works
Vullo, D., Leewattanapasuk, W., Mühlschlegel, F. A., Mastrolorenzo, A., Capasso, C., & Supuran, C. T. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.02.092 · Cited by 46 · see citing works
Innocenti, A., Leewattanapasuk, W., Mühlschlegel, F. A., Mastrolorenzo, A., & Supuran, C. T. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.06.048 · Cited by 46 · see citing works
Nishimori, I., Vullo, D., Minakuchi, T., Scozzafava, A., Capasso, C., & Supuran, C. T. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.04.006 · Cited by 45 · see citing works
Lehneck, R., Neumann, P., Vullo, D., Elleuche, S., Supuran, C. T., Ficner, R., & Pöggeler, S. (2014) · FEBS Journal · doi:10.1111/febs.12738 · Cited by 44 · see citing works
Mechanisms of unisexual mating in Cryptococcus neoformans
Wang, L., & Lin, X. (2011) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2011.02.001 · Cited by 44 · see citing works
Elleuche, S., & Pöggeler, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005177 · Cited by 44 · see citing works
Jung, K., Kim, S., Okagaki, L. H., Nielsen, K., & Bahn, Y. (2010) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2010.10.006 · Cited by 42 · see citing works
Self-citationNishimori, I., Vullo, D., Minakuchi, T., Morimoto, K., Onishi, S., Scozzafava, A., & Supuran, C. T. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.01.044 · Cited by 40 · see citing works
Innocenti, A., Zimmerman, S. A., Scozzafava, A., Ferry, J. G., & Supuran, C. T. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.10.005 · Cited by 39 · see citing works
Lin, J., Zhao, Y., Ferraro, A. R., Yang, E., Lewis, Z., & Lin, X. (2019) · Communications Biology · doi:10.1038/s42003-019-0665-2 · Cited by 38 · see citing works
Genetic basis for coordination of meiosis and sexual structure maturation in Cryptococcus neoformans
Liu, L., He, G., Chen, L., Zheng, J., Chen, Y., Shen, L., Tian, X., Li, E., Yang, E., Liao, G., et al. (2018) · eLife · doi:10.7554/elife.38683 · Cited by 38 · see citing works
Lü, Y., Su, C., Ray, S., Yuan, Y., & Liu, H. (2019) · mBio · doi:10.1128/mbio.02320-18 · Cited by 38 · see citing works
Bioinformatic analysis of beta carbonic anhydrase sequences from protozoans and metazoans
Emameh, R. Z., Barker, H. R., Tolvanen, M. E. E., Ortutay, C., & Parkkila, S. (2014) · Parasites & Vectors · doi:10.1186/1756-3305-7-38 · Cited by 38 · see citing works
Chadwick, B. J., Pham, T., Xie, X., Ristow, L. C., Krysan, D. J., & Lin, X. (2022) · eLife · doi:10.7554/elife.82563 · Cited by 35 · see citing works
Carta, F., Innocenti, A., Hall, R. A., Mühlschlegel, F. A., Scozzafava, A., & Supuran, C. T. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.02.057 · Cited by 35 · see citing works
Chapter 6 Molecular Networks in the Fungal Pathogen Candida albicans
Hall, R. A., Cottier, F., & Mühlschlegel, F. A. (2009) · Advances in applied microbiology · doi:10.1016/s0065-2164(08)01006-x · Cited by 34 · see citing works
Langereis, J. D., Zomer, A., Stunnenberg, H. G., Burghout, P., & Hermans, P. W. M. (2013) · Journal of Bacteriology · doi:10.1128/jb.01870-12 · Cited by 33 · see citing works
CO2 sensing in fungi: at the heart of metabolic signaling
Martin, R., Pohlers, S., Mühlschlegel, F. A., & Kurzai, O. (2017) · Current Genetics · doi:10.1007/s00294-017-0700-0 · Cited by 33 · see citing works
Krysan, D. J., Zhai, B., Beattie, S. R., Misel‐Wuchter, K., Wellington, M. A., & Lin, X. (2019) · mBio · doi:10.1128/mbio.01410-19 · Cited by 33 · see citing works
Hall, R. A., Vullo, D., Innocenti, A., Scozzafava, A., Supuran, C. T., Klappa, P., & Mühlschlegel, F. A. (2008) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2008.06.013 · Cited by 33 · see citing works
Streptococcus pneumoniae Folate Biosynthesis Responds to Environmental CO2Levels
Burghout, P., Zomer, A., Jongh, C. E. V. D. G., Janssen‐Megens, E. M., Françoijs, K., Stunnenberg, H. G., & Hermans, P. W. M. (2013) · Journal of Bacteriology · doi:10.1128/jb.01942-12 · Cited by 32 · see citing works
Moreira, A. L. E., de Oliveira, M. A. P., Silva, L. O. S., Inácio, M. M., Bailão, A. M., Parente-Rocha, J. A., Cruz-Leite, V. R. M., Paccez, J. D., Soares, C. M. D. A., Weber, S. S., et al. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02968 · Cited by 31 · see citing works
Han, K., Chun, Y., De Castro Pimentel Figueiredo, B., Soriani, F. M., Savoldi, M., Almeida, A., Rodrigues, F., Cairns, C. T., Bignell, E., Tobal, J. M., et al. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07058.x · Cited by 30 · see citing works
Self-citationVullo, D., Prete, S. D., Capasso, C., & Supuran, C. T. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.01.078 · Cited by 29 · see citing works
Isatin analogs as novel inhibitors of Candida spp. β-carbonic anhydrase enzymes
Akdemir, A., Güzel-Akdemir, Ö., Karalı, N., & Supuran, C. T. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.02.036 · Cited by 29 · see citing works
Castilho, D. G., Chaves, A. F. A., Xander, P. B., Zelanis, A., Kitano, E. S., Serrano, S. M. T., Tashima, A. K., & Batista, W. L. (2014) · Journal of Proteome Research · doi:10.1021/pr5002274 · Cited by 30 · see citing works
Hicks, J. K., & Heitman, J. (2006) · Eukaryotic Cell · doi:10.1128/ec.00213-06 · Cited by 26 · see citing works
Self-citationYan, J., Tong, Z., Liu, Y., Li, Y., Zhao, C., Mukhtar, I., Tao, Y., Chen, B., Deng, Y.-J., & Xie, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235923 · Cited by 25 · see citing works
Işık, S., KOCKAR, F. T., Aydın, M., Arslan, O., Güler, Ö. Ö., Innocenti, A., Scozzafava, A., & Supuran, C. T. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.01.105 · Cited by 25 · see citing works
Review on fungal enzyme inhibitors – potential drug targets to manage human fungal infections
Ramakrishnan, J., Rathore, S. S., & Raman, T. (2016) · RSC Advances · doi:10.1039/c6ra01577h · Cited by 27 · see citing works
Alafeefy, A. M., Işık, S., Al‐Jaber, N. A., Vullo, D., Abdel‐Aziz, H. A., Ashour, A. E., Awaad, A. S., Capasso, C., & Supuran, C. T. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.04.028 · Cited by 24 · see citing works
- 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 › Epidemiology › 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
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