Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation
Open accessAbstract
Cryptococcus neoformans is a major life-threatening fungal pathogen. In response to the stress of the host environment, C. neoformans produces large polyploid titan cells. Titan cell production enhances the virulence of C. neoformans , yet whether the polyploid aspect of titan cells is specifically influential remains unknown. We show that titan cells were more likely to survive and produce offspring under multiple stress conditions than typical cells and that even their normally sized daughters maintained an advantage over typical cells in continued exposure to stress. Although polyploid titan cells generated haploid daughter cell progeny upon in vitro replication under nutrient-replete conditions, titan cells treated with the antifungal drug fluconazole produced fluconazole-resistant diploid and aneuploid daughter cells. Interestingly, a single titan mother cell was capable of generating multiple types of aneuploid daughter cells. The increased survival and genomic diversity of titan cell progeny promote rapid adaptation to new or high-stress conditions. IMPORTANCE The ability to adapt to stress is a key element for survival of pathogenic microbes in the host and thus plays an important role in pathogenesis. Here we investigated the predominantly haploid human fungal pathogen Cryptococcus neoformans , which is capable of ploidy and cell size increases during infection through production of titan cells. The enlarged polyploid titan cells are then able to rapidly undergo ploidy reduction to generate progeny with reduced ploidy and/or aneuploidy. Under stressful conditions, titan cell progeny have a growth and survival advantage over typical cell progeny. Understanding how titan cells enhance the rate of cryptococcal adaptation under stress conditions may assist in the development of novel drugs aimed at blocking ploidy transitions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
During cryptococcosis treatment, newly emerged polyploid titan cells produced daughter cells that were more resistant to fluconazole.
“Gerstein et al. found that, during cryptococcosis treatment, newly emerged polyploid titan cells produced daughter cells that were more resistant to fluconazole and thus adapted to the host environment.”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [56]
The Results and Discussion report that titan cells produced daughter cells with a fluconazole-resistance advantage over progeny of typical cells. However, the fluconazole experiments were conducted in culture using cells obtained from mice; the paper does not show titan cells emerging and producing resistant daughters during cryptococcosis treatment in a host. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOne mechanism of C. neoformans heteroresistance is associated with multiple types of aneuploid daughter cells produced by titan cells.
“One of its mechanisms is associated with the multiple types of aneuploid daughter cells produced by titan cells [56,140,141].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [56]
A single titan mother cell produced multiple types of aneuploid daughter cells.
“Furthermore, a single titan mother cell produced multiple types of aneuploid daughter cells, which might contribute to the survivability of progeny under different environmental stresses [56].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [56]
Multiple types of aneuploid daughter cells might contribute to survivability of progeny under different environmental stresses.
“Furthermore, a single titan mother cell produced multiple types of aneuploid daughter cells, which might contribute to the survivability of progeny under different environmental stresses [56].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [56]
The titan cell plays a key part in stress adaptation and resistance to antifungal drugs.
“The titan cell also plays a key part in stress adaptation and resistance to antifungal drugs26,150.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [26]
The drug resistance attribute of titan cells is retained in their progeny.
“An important contribution of the titan cell to drug resistance is that this attribute is retained in its progeny26.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [26]
Under fluconazole-induced stress conditions, titan daughter cells are more often aneuploid, specifically with disomy of chromosomes 1 or 4, which results in improved growth in the presence of fluconazole.
“under fluconazole-induced stress conditions they are more often aneuploid, specifically with a disomy of chromosomes 1 or 4, which results in improved growth in the presence of fluconazole26.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [26]
Titan cell populations have an increased growth advantage compared with typical haploid cells on exposure to oxidative and nitrosative stress, which is not mediated through aneuploid formation.
“titan cell populations also have an increased growth advantage compared with typical haploid cells on exposure to oxidative and nitrosative stress, which is not mediated through aneuploid formation26”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Polyploid incidence and evolution
Otto, S. P., & Whitton, J. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.401 · Cited by 2,363 · see citing works
DNA methylation and epigenetic inheritance
Holliday, R. (1990) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.1990.0015 · Cited by 2,290 · see citing works
Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells
Fujiwara, T., Bandi, M., Nitta, M., Ivanova, E. V., Bronson, R. T., & Pellman, D. (2005) · Nature · doi:10.1038/nature04217 · Cited by 1,067 · see citing works
Song, K., Lu, P., Tang, K., & Osborn, T. C. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7719 · Cited by 1,019 · see citing works
Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast
Torres, E. M., Sokolsky, T., Tucker, C. M., Chan, L. Y., Boselli, M., Dunham, M. J., & Amon, A. (2007) · Science · doi:10.1126/science.1142210 · Cited by 935 · see citing works
Cell Cycle Regulation in Plant Development
Inzé, D., & Veylder, L. D. (2006) · Annual Review of Genetics · doi:10.1146/annurev.genet.40.110405.090431 · Cited by 880 · see citing works
From polyploidy to aneuploidy, genome instability and cancer
Štorchová, Z., & Pellman, D. S. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1276 · Cited by 810 · see citing works
Aneuploidy and Isochromosome Formation in Drug-Resistant <i>Candida albicans</i>
Selmecki, A., Forche, A., & Berman, J. (2006) · Science · doi:10.1126/science.1128242 · Cited by 733 · see citing works
Self-citationCavalier‐Smith, T. (1978) · Journal of Cell Science · doi:10.1242/jcs.34.1.247 · Cited by 683 · see citing works
Ploidy Regulation of Gene Expression
Galitski, T., Saldanha, A. J., Styles, C. A., Lander, E. S., & Fink, G. R. (1999) · Science · doi:10.1126/science.285.5425.251 · Cited by 633 · see citing works
Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast
Pavelka, N., Rancati, G., Zhu, J., Bradford, W. D., Saraf, A., Florens, L., Sanderson, B. W., Hattem, G. L., & Li, R. (2010) · Nature · doi:10.1038/nature09529 · Cited by 577 · see citing works
Sionov, E., Lee, H., Chang, Y. C., & Kwon-Chung, K. J. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000848 · Cited by 479 · see citing works
Chromosomal Instability Confers Intrinsic Multidrug Resistance
Lee, A. J. X., Endesfelder, D., Rowan, A., Walther, A., Birkbak, N. J., Futreal, P. A., Downward, J., Szállási, Z., Tomlinson, I. P. M., Howell, M. T., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3604 · Cited by 466 · see citing works
Mechanisms of genomic rearrangements and gene expression changes in plant polyploids
Chen, Z. J., & Ni, Z. (2006) · BioEssays · doi:10.1002/bies.20374 · Cited by 432 · see citing works
Sexual Cycle of Cryptococcus neoformans var. grubii and Virulence of Congenic a and α Isolates
Nielsen, K., Cox, G. M., Wang, P., Toffaletti, D. L., Perfect, J. R., & Heitman, J. (2003) · Infection and Immunity · doi:10.1128/iai.71.9.4831-4841.2003 · Cited by 383 · see citing works
Self-citationGenome-wide genetic analysis of polyploidy in yeast
Štorchová, Z., Breneman, A., Cande, J., Dunn, J. G., Burbank, K. S., O'Toole, E. T., & Pellman, D. S. (2006) · Nature · doi:10.1038/nature05178 · Cited by 360 · see citing works
Galipeau, P. C., Cowan, D., Sanchez, C. A., Barrett, M. T., Emond, M. J., Levine, D. S., Rabinovitch, P. S., & Reid, B. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.7081 · Cited by 360 · see citing works
Kelly, S. L., Lamb, D. C., Kelly, D. E., Manning, N. J., Loeffler, J., Hebart, H., Schumacher, U., & Einsele, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01360-9 · Cited by 351 · see citing works
Cryptococcal cell morphology affects host cell interactions and pathogenicity
Okagaki, L. H., Strain, A. K., Nielsen, J. N., Charlier, C., Baltes, N. J., Chrétien, F., Heitman, J., Dromer, F., & Nielsen, K. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000953 · Cited by 345 · see citing works
Self-citationExpanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box
Kronstad, J. W., Attarian, R., Cadieux, B., Choi, J., D’Souza, C. A., Griffiths, E., Geddes, J. M. H., Hu, G., Jung, W. H., Kretschmer, M., et al. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2522 · Cited by 340 · see citing works
Deciphering 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-citationRancati, G. I., Pavelka, N., Fleharty, B., Noll, A. C., Trimble, R., Walton, K., Perera, A. G., Staehling‐Hampton, K., Seidel, C. W., & Li, R. (2008) · Cell · doi:10.1016/j.cell.2008.09.039 · Cited by 335 · see citing works
Selmecki, A., Gerami‐Nejad, M., Paulson, C., Forche, A., & Berman, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06176.x · Cited by 325 · see citing works
Self-citationSelmecki, A. M., Dulmage, K., Cowen, L. E., Anderson, J. B., & Berman, J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000705 · Cited by 319 · see citing works
Self-citationFungal cell gigantism during mammalian infection
Zaragoza, O., García-Rodas, R., Nosanchuk, J. D., Cuenca-Estrella, M., Rodríguez-Tudela, J. L., & Casadevall, A. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000945 · Cited by 311 · see citing works
Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy
Chen, G., Bradford, W. D., Seidel, C. W., & Li, R. (2012) · Nature · doi:10.1038/nature10795 · Cited by 274 · see citing works
Mating-Type Locus of Cryptococcus neoformans : a Step in the Evolution of Sex Chromosomes
Lengeler, K. B., Fox, D. S., Fraser, J. A., Allen, A., Forrester, K., Dietrich, F. S., & Heitman, J. (2002) · Eukaryotic Cell · doi:10.1128/ec.1.5.704-718.2002 · Cited by 266 · see citing works
Self-citationTetraploidy and chromosomal instability are early events during cervical carcinogenesis
Olaharski, A. J., Sotelo, R., Solorza-Luna, G., Gonsebatt, M. E., Guzmán, P., Mohar, A., & Eastmond, D. A. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi218 · Cited by 264 · 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
Self-citationApoptosis regulation in tetraploid cancer cells
Castedo, M., Coquelle, A., Vivet, S., Vitale, I., Kauffmann, A., Dessen, P., Péquignot, M. O., Casares, N., Valent, A., Mouhamad, S., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601127 · Cited by 206 · see citing works
Lengeler, K. B., Cox, G. M., & Heitman, J. (2001) · Infection and Immunity · doi:10.1128/iai.69.1.115-122.2001 · Cited by 206 · see citing works
New Insights into the Troubles of Aneuploidy
Siegel, J. J., & Amon, A. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155807 · Cited by 204 · 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
Self-citationA Tetraploid Intermediate Precedes Aneuploid Formation in Yeasts Exposed to Fluconazole
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
Self-citationTitan Cells Confer Protection from Phagocytosis in Cryptococcus neoformans Infections
Okagaki, L. H., & Nielsen, K. (2012) · Eukaryotic Cell · doi:10.1128/ec.00121-12 · Cited by 173 · see citing works
Self-citationMetabolic adaptation in Cryptococcus neoformans during early murine pulmonary infection
Hu, G., Cheng, P.-Y., Sham, A. P., Perfect, J. R., & Kronstad, J. W. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06374.x · Cited by 170 · see citing works
Physiological significance of polyploidization in mammalian cells.
Pandit, S. K., Westendorp, B., & de Bruin, A. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.06.002 · Cited by 165 · see citing works
Spontaneous Mutations in Diploid Saccharomyces cerevisiae
Joseph, S., & Hall, D. W. (2004) · Genetics · doi:10.1534/genetics.104.033761 · Cited by 165 · see citing works
High levels of chromosome instability in polyploids of Saccharomyces cerevisiae
Mayer, V. W., & Aguilera, A. (1990) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(90)90024-x · Cited by 160 · see citing works
Ni, M., Feretzaki, M., Li, W., Averette, A. F., Mieczkowski, P. A., Dietrich, F. S., & Heitman, J. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001653 · Cited by 155 · see citing works
Abbey, D. A., Funt, J., Lurie-Weinberger, M. N., Thompson, D. A., Regev, A., Myers, C. L., & Berman, J. (2014) · Genome Medicine · doi:10.1186/s13073-014-0100-8 · Cited by 147 · see citing works
Self-citationTitan 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
Self-citationA general lack of compensation for gene dosage in yeast
Springer, M., Weissman, J. S., & Kirschner, M. W. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.19 · Cited by 122 · see citing works
The evolution of haploidy and diploidy
Otto, S. P., & Gerstein, A. C. (2008) · Current Biology · doi:10.1016/j.cub.2008.09.039 · Cited by 121 · see citing works
Self-citationOkagaki, 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
Self-citationSionov, E., Chang, Y. C., & Kwon-Chung, K. J. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00694-13 · Cited by 112 · see citing works
Dr Jekyll and Mr Hyde: role of aneuploidy in cellular adaptation and cancer
Pavelka, N., Rancati, G. I., & Li, R. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.06.003 · Cited by 110 · see citing works
Duesberg, P., Stindl, R., & Hehlmann, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201398998 · Cited by 106 · see citing works
Katz-Ezov, T., Nadjar-Boger, E., Frenkel, Z., Katsperovski, I., Kemeny, S., Nevo, E., Korol, A., & Kashi, Y. (2006) · Genetics · doi:10.1534/genetics.106.062745 · Cited by 100 · 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
Mixed Infections and In Vivo Evolution in the Human Fungal Pathogen Cryptococcus neoformans
Desnos‐Ollivier, M., Patel, S., Spaulding, A. R., et al. (2010) · mBio · doi:10.1128/mbio.00091-10 · Cited by 98 · see citing works
The Fitness Consequences of Aneuploidy Are Driven by Condition-Dependent Gene Effects
Sunshine, A. B., Payen, C., Ong, G. T., Liachko, I., Tan, K. M., & Dunham, M. J. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002155 · Cited by 93 · see citing works
Lv, L., Zhang, T., Yi, Q., Huang, Y., Wang, Z., Hou, H., Zhang, H., Zheng, W., Hao, Q., Guo, Z., et al. (2012) · Cell Cycle · doi:10.4161/cc.21196 · Cited by 89 · see citing works
Correction: Fungal Cell Gigantism during Mammalian Infection
Zaragoza, O., García-Rodas, R., Nosanchuk, J. D., Cuenca-Estrella, M., Rodríguez-Tudela, J. L., & Casadevall, A. (2010) · PLoS Pathogens · doi:10.1371/annotation/0675044c-d80f-456f-bb63-4f85fb1d0c33 · Cited by 83 · see citing works
Cryptococcus 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
Large 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
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
Microarray analysis of gene expression of mouse hepatocytes of different ploidy
Lü, P., Prost, S., Caldwell, H., Tugwood, J. D., Betton, G. R., & Harrison, D. J. (2007) · Mammalian Genome · doi:10.1007/s00335-007-9048-y · Cited by 69 · see citing works
Ormerod, K. L., Morrow, C. A., Chow, E. W. L., Lee, I. R., Arras, S. D. M., Schirra, H. J., Cox, G. M., Fries, B. C., & Fraser, J. A. (2013) · G3 Genes Genomes Genetics · doi:10.1534/g3.113.005660 · Cited by 65 · see citing works
Self-citationNgamskulrungroj, P., Chang, Y., Hansen, B., Bugge, C., Fischer, E., & Kwon-Chung, K. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033022 · Cited by 56 · see citing works
Methods for comparing Salmonella mutagenicity data sets using nonlinear models
Alvord, W. G., Driver, J., Claxton, L. D., et al. (1990) · Mutation Research/Genetic Toxicology · doi:10.1016/0165-1218(90)90057-9 · Cited by 53 · see citing works
Rapid extraction of fungal DNA from clinical samples for PCR amplification
Velegraki, A., Kambouris, M. E., Kostourou, A., Chalevelakis, G., & Legakis, N. J. (1999) · Medical Mycology · doi:10.1080/02681219980000101 · Cited by 49 · see citing works
Ploidy variation in multinucleate cells changes under stress
Anderson, C. A., Roberts, S. E., Zhang, H., Kelly, C. M., Kendall, A., Lee, C., Gerstenberger, J. P., Koenig, A. B., Kabeche, R., & Gladfelter, A. S. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-09-1375 · Cited by 46 · see citing works
Wang, J., Zhou, Q., Cai, H., Zhuang, Y., Zhang, Y., Xin, X.-Y., Meng, F., & Wang, Y. (2014) · Europe PMC (PubMed Central) · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationTreatment 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
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
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
Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis
Stone, N. R. H., Rhodes, J., Fisher, M. C., Mfinanga, S., Kivuyo, S., Rugemalila, J., Segal, E. S., Needleman, L., Molloy, S. F., Kwon-Chung, J., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124516 · Cited by 167 · see citing works
Self-citationExpandable and reversible copy number amplification drives rapid adaptation to antifungal drugs
Todd, R. T., & Selmecki, A. (2020) · eLife · doi:10.7554/elife.58349 · Cited by 138 · 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-citationPloidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution
Todd, R. T., Forche, A., & Selmecki, A. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0051-2016 · Cited by 121 · see citing works
Genome plasticity in Candida albicans is driven by long repeat sequences
Todd, R. T., Wikoff, T. D., Forche, A., & Selmecki, A. (2019) · eLife · doi:10.7554/elife.45954 · Cited by 118 · 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
Forche, A., Cromie, G., Gerstein, A. C., Solis, N. V., Pisithkul, T., Srifa, W., Jeffery, E., Abbey, D., Filler, S. G., Dudley, A. M., et al. (2018) · Genetics · doi:10.1534/genetics.118.301019 · Cited by 94 · see citing works
Self-citationGenetic Drivers of Multidrug Resistance in Candida glabrata
Healey, K. R., Jimenez Ortigosa, C., Shor, E., & Perlin, D. S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01995 · Cited by 93 · 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
Self-citationThe 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
A Double-Edged Sword: Aneuploidy is a Prevalent Strategy in Fungal Adaptation
Tsai, H.-J., & Nelliat, A. (2019) · Genes · doi:10.3390/genes10100787 · Cited by 60 · see citing works
Mechanisms 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
Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in <i>Candida albicans</i>
Todd, R. T., Soisangwan, N., Peters, S., Kemp, B., Crooks, T., Gerstein, A., & Selmecki, A. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad009 · Cited by 53 · see citing works
Self-citationYang, F., Gritsenko, V., Lu, H., Zhen, C., Gao, L., Berman, J., & Jiang, Y.-Y. (2021) · Microbiology Spectrum · doi:10.1128/spectrum.00723-21 · Cited by 49 · see citing works
Self-citationAltamirano, S., Fang, D., Simmons, C., Sridhar, S., Wu, P., Sanyal, K., & Kozubowski, L. (2017) · mSphere · doi:10.1128/msphere.00205-17 · Cited by 46 · see citing works
Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi
Gusa, A., & Jinks-Robertson, S. (2019) · Genes · doi:10.3390/genes10110901 · Cited by 38 · see citing works
Cao, C., Wang, K., Wang, Y., Liu, T.-B., Rivera, A., & Xue, C. (2022) · Nature Communications · doi:10.1038/s41467-022-34151-6 · Cited by 18 · see citing works
Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance
Su, Y., Li, Y., Yi, Q., Xu, Y., Sun, T., & Li, Y. (2025) · Journal of Fungi · doi:10.3390/jof11020143 · Cited by 18 · see citing works
“Furthermore, a single titan mother cell produced multiple types of aneuploid daughter cells, which might contribute to the survivability of progeny under different environmental stresses [56].”
- Authors
- Gerstein, A. C., Fu, M. S., Mukaremera, L., Li, Z., Ormerod, K. L., Fraser, J. A., Berman, J., & Nielsen, K.
- Affiliations
- University of Minnesota (US)
- The University of Queensland (AU)
- Corresponding author
- Nielsen, Kirsten
- ORCID
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2015-10-30
- Volume
- 6
- Issue
- 5
- Pages
- e01340-15
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC4620463
- OpenAlex
- W2177953885
- Cited by
- 167
- References
- 64
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 14 · 2023: 12 · 2022: 24 · 2021: 23 · 2020: 15 · 2019: 17 · 2018: 14 · 2017: 15 · 2016: 8 · 2015: 1
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Mayo Clinic
- Azrieli Foundation
- National Institutes of Health (UL1TR000114)
- National Health and Medical Research Council
- National Institute of Allergy and Infectious Diseases (R01AI080275, R01AI0624273)
- National Center for Advancing Translational Sciences
- 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, titan cells, polyploidy, aneuploidy, stress adaptation, fluconazole resistance, antifungal resistance, ploidy reduction, genomic diversity, fungal virulence, cell size
- MeSH terms
- Aneuploidy, Animals, Antifungal Agents, Cryptococcosis, Cryptococcus neoformans, Disease Models, Animal, Female, Haploidy, Mice, Inbred C57BL, Polyploidy, Stress, Physiological, Fluconazole, Drug Resistance, Fungal, Microbial Viability
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
