Fungal cell gigantism during mammalian infection
Open accessAbstract
The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.
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Unique to C. neoformans, the cell cycle is differentially regulated during the formation of polyploid titan cells, which are gigantic cells that form inside host lungs and play important roles in pathogenesis, stress responses, and drug tolerance.
“Unique to C. neoformans, the cell cycle is differentially regulated during the formation of polyploid titan cells, which are gigantic cells that form inside host lungs and play important roles in pathogenesis, stress responses, and drug tolerance (Okagaki et al. 2010; Zaragoza et al. 2010).”
From Genetic analysis of Hsp90 function in <i>Cryptococcus neoformans</i> highlights key roles in stress tolerance and virulence (2022) · cites this paper as Zaragoza et al. 2010
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Cites
Classification and Regression Trees.
Gordon, A. D., Breiman, L., Friedman, J. H., Olshen, R. A., & Stone, C. J. (1984) · Biometrics · doi:10.2307/2530946 · Cited by 23,834 · see citing works
Classification and Regression Trees.
Ryzin, J. V., Breiman, L., Friedman, J. H., Olshen, R. A., & Stone, C. J. (1986) · Journal of the American Statistical Association · doi:10.2307/2288003 · Cited by 21,028 · see citing works
Classification And Regression Trees
Breiman, L., Friedman, J. H., Olshen, R. A., & Stone, C. J. (2017) · doi:10.1201/9781315139470 · Cited by 11,417 · see citing works
Classification and regression trees
Praagman, J. (1985) · European Journal of Operational Research · doi:10.1016/0377-2217(85)90321-2 · Cited by 10,053 · see citing works
Park, B. J., Wannemuehler, K. A., Marston, B. J., Govender, N. P., Pappas, P. G., & Chiller, T. M. (2009) · AIDS · doi:10.1097/qad.0b013e328322ffac · Cited by 2,013 · see citing works
de Hoog, S., Guarro, J., Gené, J., & Figueras, M. J. (2000) · UvA-DARE (University of Amsterdam) · Cited by 1,427 · see citing works
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 · see citing works
Cavalier‐Smith, T. (1978) · Journal of Cell Science · doi:10.1242/jcs.34.1.247 · Cited by 683 · see citing works
The damage-response framework of microbial pathogenesis
Casadevall, A., & Pirofski, L. (2003) · Nature Reviews Microbiology · doi:10.1038/nrmicro732 · Cited by 662 · see citing works
Self-citation“Big it up”: endoreduplication and cell-size control in plants
Sugimoto, K., & Roberts, K. (2003) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2003.09.009 · Cited by 577 · see citing works
Eukaryotic control on bacterial cell cycle and differentiation in the Rhizobium –legume symbiosis
Mergaert, P., Uchiumi, T., Alunni, B., Evanno, G., Cheron, A., Catrice, O., Mausset, A.-E., Barloy-Hubler, F., Galibert, F., Kondorosi, Á., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600912103 · Cited by 501 · see citing works
Chapter 4 The Capsule of the Fungal Pathogen Cryptococcus neoformans
Zaragoza, Ó., Rodrigues, M. L., Jesus, M. D., Frasés, S., Dadachova, E., & Casadevall, A. (2009) · Advances in applied microbiology · doi:10.1016/s0065-2164(09)01204-0 · Cited by 458 · see citing works
Self-citation<i>Cryptococcus neoformans</i>Is a Facultative Intracellular Pathogen in Murine Pulmonary Infection
Feldmesser, M., Kress, Y., Novikoff, P., & Casadevall, A. (2000) · Infection and Immunity · doi:10.1128/iai.68.7.4225-4237.2000 · Cited by 423 · see citing works
Self-citationPhagosome Extrusion and Host-Cell Survival after Cryptococcus neoformans Phagocytosis by Macrophages
Alvarez, M., & Casadevall, A. (2006) · Current Biology · doi:10.1016/j.cub.2006.09.061 · Cited by 414 · see citing works
Self-citationMorphogenesis in Candida albicans
Whiteway, M. S., & Bachewich, C. (2007) · Annual Review of Microbiology · doi:10.1146/annurev.micro.61.080706.093341 · Cited by 390 · see citing works
Charlier, C., Nielsen, K., Daou, S., Brigitte, M., Chretien, F., & Dromer, F. (2009) · Infection and Immunity · doi:10.1128/iai.01065-08 · Cited by 362 · see citing works
Morphogenesis of Filobasidiella neoformans, the Sexual State of Cryptococcus neoformans
Kwon-Chung, K. J. (1976) · Mycologia · doi:10.2307/3758800 · Cited by 352 · see citing works
Plant cell-size control: growing by ploidy?
Kondorosi, É., Roudier, F., & Gendreau, E. (2000) · Current Opinion in Plant Biology · doi:10.1016/s1369-5266(00)00118-7 · Cited by 348 · see citing works
D’Souza, C. A., Alspaugh, J. A., Yue, C., Harashima, T., Cox, G. M., Perfect, J. R., & Heitman, J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.9.3179-3191.2001 · Cited by 318 · see citing works
Expulsion of Live Pathogenic Yeast by Macrophages
Ma, H., Croudace, J. E., Lammas, D. A., & May, R. C. (2006) · Current Biology · doi:10.1016/j.cub.2006.09.032 · Cited by 310 · see citing works
Casadevall, A., Cleare, W., Feldmesser, M., Glatman-Freedman, A., Goldman, D. L., Kozel, T. R., Lendvai, N., Mukherjee, J., Pirofski, L.-A., Rivera, J., et al. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.6.1437 · Cited by 298 · see citing works
Self-citationChronic cryptococcal meningitis: a new experimental model in rabbits.
Perfect, J. R., Lang, S. D. R., & Durack, D. T. (1980) · PubMed · Cited by 283 · see citing works
Zaragoza, Ó., Chrisman, C. J., Castelli, M. V., Frasés, S., Cuenca‐Estrella, M., Rodrı́guez-Tudela, J. L., & Casadevall, A. (2008) · Cellular Microbiology · doi:10.1111/j.1462-5822.2008.01186.x · Cited by 252 · see citing works
Self-citationTranscriptional control of dimorphism in Candida albicans
Liu, H. (2001) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(01)00275-2 · Cited by 244 · see citing works
Warnock, D. W. (1999) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/44.1.139 · Cited by 232 · see citing works
Experimental modulation of capsule size in Cryptococcus neoformans
Zaragoza, Ó., & Casadevall, A. (2004) · Biological Procedures Online · doi:10.1251/bpo68 · Cited by 231 · see citing works
Self-citationRAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans
Alspaugh, J. A., Cavallo, L. M., Perfect, J. R., & Heitman, J. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01852.x · Cited by 226 · see citing works
Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection
Feldmesser, M., Kress, Y., & Casadevall, A. (2001) · Microbiology · doi:10.1099/00221287-147-8-2355 · Cited by 220 · see citing works
Self-citationAlspaugh, J. A., Pukkila-Worley, R., Harashima, T., Cavallo, L. M., Funnell, D. L., Cox, G. M., Perfect, J. R., Kronstad, J. W., & Heitman, J. (2002) · Eukaryotic Cell · doi:10.1128/ec.1.1.75-84.2002 · Cited by 196 · see citing works
Maresca, B., & Kobayashi, G. S. (1989) · Microbiological Reviews · doi:10.1128/mr.53.2.186-209.1989 · Cited by 169 · see citing works
Extreme polyploidy in a large bacterium
Mendell, J., Clements, K. D., Choat, J. H., & Angert, E. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707522105 · Cited by 149 · see citing works
Moyrand, F., Fontaine, T., & Janbon, G. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05695.x · Cited by 149 · see citing works
Synthesis of Polymerized Melanin byCryptococcus neoformansin Infected Rodents
Rosas, Á. L., Nosanchuk, J. D., Feldmesser, M., Cox, G. M., McDade, H. C., & Casadevall, A. (2000) · Infection and Immunity · doi:10.1128/iai.68.5.2845-2853.2000 · Cited by 149 · see citing works
Self-citationMelanisation of Cryptococcus neoformans in human brain tissue
Nosanchuk, J. D., Rosas, Á. L., Lee, S. C., & Casadevall, A. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02356-4 · Cited by 134 · see citing works
Self-citationAlvarez, M., & Casadevall, A. (2007) · BMC Immunology · doi:10.1186/1471-2172-8-16 · Cited by 131 · see citing works
Self-citationYauch, L. E., Lam, J. S., & Levitz, S. (2006) · PLoS Pathogens · doi:10.1371/journal.ppat.0020120 · Cited by 130 · see citing works
Kechichian, T. B., Shea, J., & Del Poeta, M. (2007) · Infection and Immunity · doi:10.1128/iai.00587-07 · Cited by 128 · see citing works
Melanization of Cryptococcus neoformans in Murine Infection
Nosanchuk, J. D., Valadon, P., Feldmesser, M., & Casadevall, A. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.745 · Cited by 127 · see citing works
Self-citationMolecular architecture of the Cryptococcus neoformans capsule
Gates, M. A., Thorkildson, P., & Kozel, T. R. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2003.03957.x · Cited by 126 · see citing works
Shao, X., Mednick, A., Alvarez, M., van Rooijen, N., Casadevall, A., & Goldman, D. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.5.3244 · Cited by 124 · see citing works
Self-citationZaragoza, Ó., Taborda, C. P., & Casadevall, A. (2003) · European Journal of Immunology · doi:10.1002/eji.200323848 · Cited by 123 · see citing works
Self-citationGoldman, D. L., Lee, S. C., & Casadevall, A. (1995) · Infection and Immunity · doi:10.1128/iai.63.9.3448-3453.1995 · Cited by 114 · see citing works
Self-citationShea, J. M., Kechichian, T. B., Luberto, C., & Del Poeta, M. (2006) · Infection and Immunity · doi:10.1128/iai.00768-06 · Cited by 110 · see citing works
Zaragoza, Ó., Alvarez, M., Telzak, A., Rivera, J., & Casadevall, A. (2007) · Infection and Immunity · doi:10.1128/iai.00094-07 · Cited by 100 · see citing works
Self-citationEstimating the Relative Contributions of Virulence Factors for Pathogenic Microbes
McClelland, E. E., Bernhardt, P. C., & Casadevall, A. (2006) · Infection and Immunity · doi:10.1128/iai.74.3.1500-1504.2006 · Cited by 100 · see citing works
Self-citationDirect cell-to-cell spread of a pathogenic yeast
Ma, H., Croudace, J. E., Lammas, D. A., & May, R. C. (2007) · BMC Immunology · doi:10.1186/1471-2172-8-15 · Cited by 96 · see citing works
Rodrigues, M. L., Alvarez, M., Fonseca, F. L., & Casadevall, A. (2007) · Eukaryotic Cell · doi:10.1128/ec.00307-07 · Cited by 96 · see citing works
Self-citationLee, S. C., Casadevall, A., & Dickson, D. W. (1996) · PubMed · Cited by 91 · see citing works
Self-citationMaresca, B., & Kobayashi, G. S. (1989) · Microbiological Reviews · doi:10.1128/mmbr.53.2.186-209.1989 · Cited by 89 · see citing works
Zaragoza, Ó., Telzak, A., Bryan, R. A., Dadachova, E., & Casadevall, A. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04928.x · Cited by 87 · see citing works
Self-citationCryptococcus neoformans of Unusual Morphology
Cruickshank, J. G., Cavill, R. H., & Jelbert, M. (1973) · Applied Microbiology · doi:10.1128/am.25.2.309-312.1973 · Cited by 78 · see citing works
Bryan, R. A., Zaragoza, Ó., Zhang, T., Ortiz, G., Casadevall, A., & Dadachova, E. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.2.465-475.2005 · Cited by 78 · see citing works
Self-citationLarge Cryptococcus neoformans isolated from brain abscess
Love, G., Boyd, G., & Greer, D. L. (1985) · Journal of Clinical Microbiology · doi:10.1128/jcm.22.6.1068-1070.1985 · Cited by 77 · see citing works
The volume and hydration of the Cryptococcus neoformans polysaccharide capsule
Maxson, M. E., Cook, E., Casadevall, A., & Zaragoza, Ó. (2006) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2006.07.010 · Cited by 66 · see citing works
Self-citationGlatman‐Freedman, A., Martin, J., Riska, P. F., Bloom, B. R., & Casadevall, A. (1996) · Journal of Clinical Microbiology · doi:10.1128/jcm.34.11.2795-2802.1996 · Cited by 65 · see citing works
Self-citationSoluble Polysaccharides of Cryptococcus neoformans
Cherniak, R. (1988) · Current topics in medical mycology · doi:10.1007/978-1-4612-3730-3_2 · Cited by 59 · see citing works
Radial Mass Density, Charge, and Epitope Distribution in theCryptococcus neoformansCapsule
Maxson, M. E., Dadachova, E., Casadevall, A., & Zaragoza, Ó. (2006) · Eukaryotic Cell · doi:10.1128/ec.00306-06 · Cited by 55 · see citing works
Self-citationGarcía-Rivera, J., Eisenman, H. C., Nosanchuk, J. D., Aisen, P., Zaragoza, Ó., Moadel, T., Dadachova, E., & Casadevall, A. (2005) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2005.09.003 · Cited by 51 · see citing works
Self-citationCryptococcus neoformans of Unusual Morphology
Cruickshank, J. G., Cavill, R. H., & Jelbert, M. (1973) · Applied Microbiology · doi:10.1128/aem.25.2.309-312.1973 · Cited by 49 · see citing works
Cleare, W., & Casadevall, A. (1999) · Medical Mycology · doi:10.1046/j.1365-280x.1999.00226.x · Cited by 39 · see citing works
Self-citationDimorphism in Histoplasma capsulatum and Blastomyces dermatitidis
Maresca, B., & Kobayashi, G. S. (2000) · KARGER eBooks · doi:10.1159/000060346 · Cited by 38 · see citing works
Zaragoza, Ó., & Casadevall, A. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00753.x · Cited by 36 · see citing works
Self-citationCell Size Control: New Evidence for a General Mechanism
Grebien, F., Dolznig, H., Beug, H., & Müllner, E. W. (2005) · Cell Cycle · doi:10.4161/cc.4.3.1523 · Cited by 31 · see citing works
Fungal Capsular Polysaccharide and T-Cell Suppression: The Hidden Nature of Poor Immunogenicity
Vecchiarelli, A. (2007) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v27.i6.50 · Cited by 31 · see citing works
Conversion of Blastomyces dermatitidis to the yeast form at 37 degrees C and 26 degrees C
Kane, J. (1984) · Journal of Clinical Microbiology · doi:10.1128/jcm.20.3.594-596.1984 · Cited by 28 · see citing works
Chaskes, S., Frasés, S., Cammer, M., Gerfen, G. J., & Casadevall, A. (2007) · Journal of Clinical Microbiology · doi:10.1128/jcm.01721-07 · Cited by 24 · see citing works
Self-citationControl of Cell Cycle and Cell Growth by Molecular Chaperones
Aldea, M., Garí, E., & Colomina, N. (2007) · Cell Cycle · doi:10.4161/cc.6.21.4920 · Cited by 22 · see citing works
Biological and electron microscopic changes in gamma radiated Cryptococcus neoformans
Dembitzer, H. M., Buza, I., & Reiss, F. (1972) · Mycopathologia et Mycologia Applicata · doi:10.1007/bf02051669 · Cited by 18 · see citing works
The Outcome of Phagocytic Cell Division with Infectious Cargo Depends on Single Phagosome Formation
Luo, Y., Alvarez, M., Xia, L., & Casadevall, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003219 · Cited by 18 · see citing works
Self-citationEffect of Amphotericin B on Capsule and Cell Size inCryptococcus neoformansduring Murine Infection
Zaragoza, Ó., Mihu, C. N., Casadevall, A., & Nosanchuk, J. D. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.10.4358-4361.2005 · Cited by 16 · see citing works
Self-citationGiant Blastoconidia of Candida albicans
Alasio, T. M., Lento, P. A., & Bottone, E. J. (2003) · Archives of Pathology & Laboratory Medicine · doi:10.5858/2003-127-868-gboca · Cited by 13 · see citing works
Scanning electron microscope studies on the parasitic cycle of Coccidioides immitis
Miyaji, M., Nishimura, K., & Ajello, L. (1985) · Mycopathologia · doi:10.1007/bf00437133 · Cited by 11 · see citing works
Bottone, E. J., Horga, M.-A., & Abrams, J. (1999) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/s0732-8893(99)00013-9 · Cited by 9 · see citing works
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The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species
Garcia-Rubio, R., de Oliveira, H. C., Rivera, J., & Trevijano-Contador, N. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02993 · Cited by 917 · see citing works
Maziarz, E. K., & Perfect, J. R. (2016) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2015.10.006 · Cited by 698 · see citing works
Regulatory 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 · see citing works
Cryptococcus: from environmental saprophyte to global pathogen
May, R. C., Stone, N. R. H., Wiesner, D. L., Bicanic, T., & Nielsen, K. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2015.6 · Cited by 541 · see citing works
The 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
Treatment strategies for cryptococcal infection: challenges, advances and future outlook
Iyer, K. R., Revie, N. M., Fu, C., Robbins, N., & Cowen, L. E. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00511-0 · Cited by 363 · see citing works
The Spectrum of Fungi That Infects Humans
Kohler, J. R., Casadevall, A., & Perfect, J. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019273 · Cited by 364 · see citing works
Self-citationCryptococcal 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
Expanding 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
Köhler, J. R., Hube, B., Puccia, R., Casadevall, A., & Perfect, J. R. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0014-2016 · Cited by 301 · see citing works
Self-citationStaying in Shape: the Impact of Cell Shape on Bacterial Survival in Diverse Environments
Yang, D. C., Blair, K. M., & Salama, N. R. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00031-15 · Cited by 283 · see citing works
Pulmonary cryptococcosis: A review of pathobiology and clinical aspects
Setianingrum, F., Rautemaa‐Richardson, R., & Denning, D. W. (2018) · Medical Mycology · doi:10.1093/mmy/myy086 · Cited by 293 · see citing works
Basic principles of the virulence of <i>Cryptococcus</i>
Zaragoza, O. (2019) · Virulence · doi:10.1080/21505594.2019.1614383 · Cited by 249 · see citing works
Polyploidy in fungi: evolution after whole-genome duplication
Albertin, W., & Marullo, P. (2012) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2012.0434 · Cited by 248 · see citing works
Wiesner, D. L., Specht, C. A., Lee, C. K., Smith, K. D., Mukaremera, L., Lee, S. T., Lee, C. G., Elias, J. A., Nielsen, J. N., Boulware, D. R., et al. (2015) · PLOS Pathogens · doi:10.1371/journal.ppat.1004701 · Cited by 214 · see citing works
The expanding implications of polyploidy
Schoenfelder, K. P., & Fox, D. T. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201502016 · Cited by 210 · see citing works
Systematic functional profiling of transcription factor networks in Cryptococcus neoformans
Jung, K., Yang, D., Maeng, S., Lee, K.-T., So, Y.-S., Hong, J., Choi, J., Byun, H.-J., Kim, H., Bang, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms7757 · Cited by 200 · see citing works
Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts
D’Souza, C. A., Kronstad, J. W., Taylor, G., Warren, R., Yuen, M., Hu, G., Jung, W. H., Sham, A., Kidd, S. E., Tangen, K., et al. (2011) · mBio · doi:10.1128/mbio.00342-10 · Cited by 202 · see citing works
Titan cells in Cryptococcus neoformans: cells with a giant impact
Zaragoza, Ó., & Nielsen, K. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.03.006 · Cited by 190 · see citing works
Hidalgo-Cantabrana, C., López, P., Gueimonde, M., Reyes‐Gavilán, C. G. D. L., Suárez, A., Margollés, A., & Ruas‐Madiedo, P. (2012) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-012-9110-2 · Cited by 192 · see citing works
Dambuza, I. M., Drake, T., Chapuis, A., Zhou, X., Correia, J., Taylor-Smith, L., LeGrave, N., Rasmussen, T., Fisher, M. C., Bicanic, T., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1006978 · Cited by 182 · see citing works
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Harrison, B. D., Hashemi, J., Bibi, M., Pulver, R., Bavli, D., Nahmias, Y., Wellington, M., Sapiro, G., & Berman, J. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001815 · Cited by 174 · see citing works
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Okagaki, L. H., & Nielsen, K. (2012) · Eukaryotic Cell · doi:10.1128/ec.00121-12 · Cited by 173 · see citing works
Lee, S. C., Li, A., Calo, S., & Heitman, J. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003625 · Cited by 172 · see citing works
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Gerstein, A. C., Fu, M. S., Mukaremera, L., Li, Z., Ormerod, K. L., Fraser, J. A., Berman, J., & Nielsen, K. (2015) · mBio · doi:10.1128/mbio.01340-15 · Cited by 167 · see citing works
Evolution of fungal sexual reproduction
Heitman, J., Sun, S., & James, T. Y. (2013) · Mycologia · doi:10.3852/12-253 · Cited by 155 · see citing works
Ngamskulrungroj, P., Chang, Y. C., Sionov, E., & Kwon-Chung, K. J. (2012) · mBio · doi:10.1128/mbio.00103-12 · Cited by 152 · see citing works
Sporangiospore Size Dimorphism Is Linked to Virulence of Mucor circinelloides
Li, C. H., Cervantes, M., Springer, D. J., Boekhout, T., Ruiz‐Vázquez, R. M., Torres‐Martínez, S., Heitman, J., & Lee, S. C. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002086 · Cited by 151 · 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
Johnston, S. A., & May, R. C. (2012) · Cellular Microbiology · doi:10.1111/cmi.12067 · Cited by 145 · see citing works
Hommel, B., Mukaremera, L., Cordero, R. J. B., Coelho, C., Desjardins, C. A., Sturny-Leclère, A., Janbon, G., Perfect, J. R., Fraser, J. A., Casadevall, A., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1006982 · Cited by 143 · see citing works
Self-citationCryptococcus neoformans: historical curiosity to modern pathogen
Srikanta, D., Santiago-Tirado, F. H., & Doering, T. L. (2013) · Yeast · doi:10.1002/yea.2997 · Cited by 140 · see citing works
Dalia, A. B., & Weiser, J. N. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.09.009 · Cited by 137 · see citing works
Immune Response of Galleria mellonella against Human Fungal Pathogens
Trevijano-Contador, N., & Zaragoza, O. (2018) · Journal of Fungi · doi:10.3390/jof5010003 · Cited by 134 · see citing works
Crosby, H. A., Kwiecinski, J. M., & Horswill, A. R. (2016) · Advances in applied microbiology · doi:10.1016/bs.aambs.2016.07.018 · Cited by 133 · see citing works
Subversion of Phagocytosis for Pathogen Survival
Sarantis, H., & Grinstein, S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.09.001 · Cited by 131 · 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
The Intracellular Life ofCryptococcus neoformans
Coelho, C., Bocca, A. L., & Casadevall, A. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104653 · Cited by 130 · see citing works
Self-citationpH Response Pathways in Fungi: Adapting to Host-derived and Environmental Signals
Ost, K. S., & Alspaugh, J. A. (2011) · Mycobiology · doi:10.5941/myco.2011.39.4.249 · Cited by 127 · see citing works
Virulence mechanisms and Cryptococcus neoformans pathogenesis
Alspaugh, J. A. (2014) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2014.09.004 · Cited by 128 · see citing works
Chrisman, C. J., Albuquerque, P., Guimaraes, A. J., Nieves, E., & Casadevall, A. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002047 · Cited by 129 · see citing works
Self-citationMechanisms of fungal dissemination
Strickland, A. B., & Shi, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03736-z · Cited by 127 · see citing works
Competitive Science: Is Competition Ruining Science?
Fang, F. C., & Casadevall, A. (2015) · Infection and Immunity · doi:10.1128/iai.02939-14 · Cited by 129 · see citing works
Self-citationO’Meara, T. R., Holmer, S. M., Ost, K. S., Dietrich, F. S., & Alspaugh, J. A. (2013) · mBio · doi:10.1128/mbio.00522-12 · Cited by 124 · 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
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Todd, R. T., Forche, A., & Selmecki, A. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0051-2016 · Cited by 121 · see citing works
Cryptococcus neoformans Host Adaptation: Toward Biological Evidence of Dormancy
Alanio, A., Vernel-Pauillac, F., Sturny-Leclère, A., & Dromer, F. (2015) · mBio · doi:10.1128/mbio.02580-14 · Cited by 119 · see citing works
Bennett, R. J., Forche, A., & Berman, J. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019604 · Cited by 118 · see citing works
Okagaki, L. H., Wang, Y., Ballou, E. R., O'Meara, T. R., Bahn, Y.-S., Alspaugh, J. A., Xue, C., & Nielsen, K. (2011) · Eukaryotic Cell · doi:10.1128/ec.05179-11 · Cited by 117 · 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
Robertson, E. J., Najjuka, G., Rolfes, M. A. R., Akampurira, A., Jain, N., Anantharanjit, J., von Hohenberg, M., Tassieri, M., Carlsson, A., Meya, D. B., et al. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit435 · Cited by 115 · see citing works
Fungal pathogens—a sweet and sour treat for toll-like receptors
Bourgeois, C., & Kuchler, K. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00142 · Cited by 114 · see citing works
Caza, M., & Kronstad, J. W. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00212 · Cited by 107 · see citing works
Cryptococcus and Phagocytes: Complex Interactions that Influence Disease Outcome
Wager, C. M. L., Hole, C. R., Wozniak, K. L., & Wormley, F. L. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00105 · Cited by 103 · see citing works
Cryptococcal pathogenic mechanisms: a dangerous trip from the environment to the brain
Esher, S. K., Zaragoza, Ó., & Alspaugh, J. A. (2018) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/0074-02760180057 · Cited by 104 · see citing works
Microbial pathogens in the fungal kingdom
Heitman, J. (2011) · Fungal Biology Reviews · doi:10.1016/j.fbr.2011.01.003 · Cited by 104 · see citing works
Toward an Integrated Model of Capsule Regulation in Cryptococcus neoformans
Haynes, B. C., Skowyra, M. L., Spencer, S. J., Gish, S. R., Williams, M., Held, E. P., Brent, M. R., & Doering, T. L. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002411 · Cited by 102 · see citing works
Qin, Q., Luo, J., Lin, X., Pei, J., Li, L., Ficht, T. A., & de Figueiredo, P. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002078 · Cited by 101 · see citing works
The cryptic sexual strategies of human fungal pathogens
Ene, I. V., & Bennett, R. J. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3236 · Cited by 99 · see citing works
The Tools for Virulence of Cryptococcus neoformans
Coelho, C., Bocca, A. L., & Casadevall, A. (2014) · Advances in applied microbiology · doi:10.1016/b978-0-12-800261-2.00001-3 · Cited by 98 · see citing works
Self-citationLife Cycle ofCryptococcus neoformans
Zhao, Y., Lin, J., Fan, Y., & Lin, X. (2019) · Annual Review of Microbiology · doi:10.1146/annurev-micro-020518-120210 · Cited by 102 · see citing works
García‐Rodas, R., Casadevall, A., Rodrı́guez-Tudela, J. L., Cuenca‐Estrella, M., & Zaragoza, Ó. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024485 · Cited by 99 · see citing works
Self-citationX-Linked Immunodeficient Mice Exhibit Enhanced Susceptibility to Cryptococcus neoformans Infection
Szymczak, W. A., Davis, M. J., Lundy, S. K., Dufaud, C. R., Olszewski, M. A., & Pirofski, L. (2013) · mBio · doi:10.1128/mbio.00265-13 · Cited by 98 · 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
Catch me if you can: phagocytosis and killing avoidance by Cryptococcus neoformans
García‐Rodas, R., & Zaragoza, Ó. (2011) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2011.00871.x · Cited by 94 · see citing works
Self-citationMorphogenesis in Fungal Pathogenicity: Shape, Size, and Surface
Wang, L., & Lin, X. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003027 · Cited by 94 · see citing works
Mechanisms of Cryptococcus neoformans-Mediated Host Damage
Casadevall, A., Coelho, C., & Alanio, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00855 · Cited by 90 · see citing works
Self-citationHuman Fungal Pathogens of Mucorales and EntomophthoralesPreprint
Mendoza, L., Vilela, R., Voelz, K., Ibrahim, A. S., Voigt, K., & Lee, S. C. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019562 · Cited by 90 · see citing works
Opportunistic yeast pathogens: reservoirs, virulence mechanisms, and therapeutic strategies
Polvi, E. J., Li, X., O’Meara, T. R., Leach, M. D., & Cowen, L. E. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1860-z · Cited by 90 · see citing works
Microrheology with Optical Tweezers: Measuring the relative viscosity of solutions ‘at a glance’
Tassieri, M., Giudice, F. D., Robertson, E. J., Jain, N., Fries, B. C., Wilson, R., Glidle, A., Greco, F., Netti, P. A., Maffettone, P. L., et al. (2015) · Scientific Reports · doi:10.1038/srep08831 · Cited by 88 · see citing works
Stress 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
Magditch, D. A., Liu, T., Xue, C., & Idnurm, A. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002936 · Cited by 85 · see citing works
Ost, K. S., O’Meara, T. R., Huda, N., Esher, S. K., & Alspaugh, J. A. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005159 · Cited by 80 · see citing works
Fungal MorphogenesisPreprint
Lin, X., Alspaugh, J. A., Liu, H., & Harris, S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019679 · Cited by 82 · see citing works
Mechanisms of Infection by the Human Fungal Pathogen Cryptococcus Neoformans
Sabiiti, W., & May, R. C. (2012) · Future Microbiology · doi:10.2217/fmb.12.102 · Cited by 81 · see citing works
What makesCryptococcus gattiia pathogen?
Bielska, E., & May, R. C. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov106 · Cited by 81 · see citing works
A dissemination-prone morphotype enhances extrapulmonary organ entry by Cryptococcus neoformans
Denham, S. T., Brammer, B., Chung, K. Y., Wambaugh, M. A., Bednarek, J. M., Guo, L., Moreau, C. T., & Brown, J. C. S. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.08.017 · Cited by 80 · see citing works
Mukaremera, L., Lee, K. K., Wagener, J., Wiesner, D. L., Gow, N. A. R., & Nielsen, K. (2018) · The Cell Surface · doi:10.1016/j.tcsw.2017.12.001 · Cited by 79 · see citing works
Mechanisms of microbial escape from phagocyte killing
Taylor-Smith, L. M., & May, R. C. (2013) · Biochemical Society Transactions · doi:10.1042/bst20130014 · Cited by 76 · see citing works
Zhai, B., Zhu, P., Foyle, D., Upadhyay, S., Idnurm, A., & Lin, X. (2013) · Infection and Immunity · doi:10.1128/iai.00259-13 · Cited by 78 · see citing works
Cardoso, N. N. R., Alviano, C. S., Blank, A. F., Romanos, M. T. V., Fonseca, B. B., Rozental, S., Rodrigues, I. A., & Alviano, D. S. (2016) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2016/5647182 · Cited by 77 · see citing works
A titanic drug resistance threat in Cryptococcus neoformans
Zafar, H., Altamirano, S., Ballou, E. R., & Nielsen, K. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.11.001 · Cited by 76 · see citing works
Choi, J., Jung, W. H., & Kronstad, J. W. (2015) · The Journal of Microbiology · doi:10.1007/s12275-015-5247-5 · Cited by 76 · see citing works
Hu, G., Wang, J., Choi, J., Jung, W. H., Liu, I., Litvintseva, A. P., Bicanic, T. A., Aurora, R., Mitchell, T. G., Perfect, J. R., et al. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-526 · Cited by 76 · see citing works
Adaptive Immunity to Cryptococcus neoformans Infections
Mukaremera, L., & Nielsen, K. (2017) · Journal of Fungi · doi:10.3390/jof3040064 · Cited by 75 · see citing works
The Dynamic Fungal Genome: Polyploidy, Aneuploidy and Copy Number Variation in Response to Stress
Vande Zande, P., Zhou, X., & Selmecki, A. (2023) · Annual Review of Microbiology · doi:10.1146/annurev-micro-041320-112443 · Cited by 70 · see citing works
Comparative Transcriptomics of the Saprobic and Parasitic Growth Phases in Coccidioides spp
Whiston, E., Wise, H. Z., Sharpton, T. J., Jui, G., Cole, G. T., & Taylor, J. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041034 · Cited by 74 · see citing works
Ploidy variation as an adaptive mechanism in human pathogenic fungi
Morrow, C. A., & Fraser, J. A. (2013) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2013.01.008 · Cited by 72 · see citing works
Capsule Growth in Cryptococcus neoformans Is Coordinated with Cell Cycle Progression
García‐Rodas, R., Cordero, R. J. B., Trevijano‐Contador, N., Janbon, G., Moyrand, F., Casadevall, A., & Zaragoza, Ó. (2014) · mBio · doi:10.1128/mbio.00945-14 · Cited by 73 · see citing works
Self-citationMayer, F. L., & Kronstad, J. W. (2017) · mBio · doi:10.1128/mbio.01537-17 · Cited by 76 · see citing works
Boral, H., Metin, B., Döğen, A., Seyedmousavi, S., & İlkit, M. (2017) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2017.10.008 · Cited by 71 · see citing works
Matsumoto, Y., Miyazaki, S., Fukunaga, D. H., Shimizu, K., Kawamoto, S., & Sekimizu, K. (2011) · Journal of Applied Microbiology · doi:10.1111/j.1365-2672.2011.05186.x · Cited by 70 · see citing works
Cordero, R. J. B., Frasés, S., Guimaraes, A. J., Rivera, J., & Casadevall, A. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07511.x · Cited by 70 · see citing works
Self-citationMechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans
Denham, S., & Brown, J. (2018) · Journal of Fungi · doi:10.3390/jof4010025 · Cited by 67 · see citing works
Zinc Limitation Induces a Hyper-Adherent Goliath Phenotype in Candida albicans
Malavia, D., Lehtovirta-Morley, L. E., Alamir, O., Weiß, E., Gow, N. A. R., Hube, B., & Wilson, D. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02238 · Cited by 66 · see citing works
Balachandra, S., Sarkar, S., & Amodeo, A. A. (2022) · Annual Review of Genetics · doi:10.1146/annurev-genet-080320-030537 · Cited by 65 · see citing works
Firacative, C., Duan, S., & Meyer, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105076 · Cited by 66 · 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
Ploidy dynamics and evolvability in fungi
Wertheimer, N. B., Stone, N. R. H., & Berman, J. G. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0461 · Cited by 63 · see citing works
- Authors
- Zaragoza, O., García-Rodas, R., Nosanchuk, J. D., Cuenca-Estrella, M., Rodríguez-Tudela, J. L., & Casadevall, A.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-06-17
- Volume
- 6
- Issue
- 6
- Pages
- e1000945
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2887474
- OpenAlex
- W2004173797
- Cited by
- 311
- References
- 71
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 12 · 2023: 16 · 2022: 21 · 2021: 19 · 2020: 17 · 2019: 16 · 2018: 24 · 2017: 23 · 2016: 19 · 2015: 22 · 2014: 20 · 2013: 21 · 2012: 30
- FWCI
- 19.14
- Type
- journal article
- Language
- en
- Update notices
- correction (2010-06-23)
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5r01hl059842-23, 5R37AI033142, HL059842, 5r37ai033142-24)
- Instituto de Salud Carlos III
- National Heart, Lung, and Blood Institute (HL-059842, R01-HL059842)
- National Institute of Allergy and Infectious Diseases (AI-033774, R37-AI033142, 5R37AI033142, R01AI033774)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Cryptococcus neoformans, giant cells, fungal morphogenesis, polyploidy, cAMP signaling, immune evasion, phagocytosis, pulmonary infection, capsules, host-pathogen interaction
- MeSH terms
- Animals, Cryptococcosis, Cryptococcus neoformans, DNA, Fungal, Female, Fluorescent Antibody Technique, Gamma Rays, Gigantism, Lung Diseases, Fungal, Mice, Inbred BALB C, Mice, Inbred C57BL, Phagosomes, RNA, Messenger, Macrophages, Alveolar, Oxidative Stress, Reverse Transcriptase Polymerase Chain Reaction, Cell Proliferation, Mice
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