Fungicide-tolerant persister formation during cryptococcal pulmonary infection
Open accessAbstract
Bacterial persisters, a subpopulation of genetically susceptible cells that are normally dormant and tolerant to bactericides, have been studied extensively because of their clinical importance. In comparison, much less is known about the determinants underlying fungicide-tolerant fungal persister formation in vivo. Here, we report that during mouse lung infection, Cryptococcus neoformans forms persisters that are highly tolerant to amphotericin B (AmB), the standard of care for treating cryptococcosis. By exploring stationary-phase indicator molecules and developing single-cell tracking strategies, we show that in the lung, AmB persisters are enriched in cryptococcal cells that abundantly produce stationary-phase molecules. The antioxidant ergothioneine plays a specific and key role in AmB persistence, which is conserved in phylogenetically distant fungi. Furthermore, the antidepressant sertraline (SRT) shows potent activity specifically against cryptococcal AmB persisters. Our results provide evidence for and the determinant of AmB-tolerant persister formation in pulmonary cryptococcosis, which has potential clinical significance.
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?
In a mouse model of pulmonary cryptococcosis, ergothioneine and its encoding gene EGT1 were significantly overexpressed in AmB persisters.
“Moreover, a recent study using a mouse model of pulmonary cryptococcosis found that ergothioneine and its encoding gene, EGT1, were significantly overexpressed in AmB persisters.”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
The Results (Figure 5C) show significantly higher ergothioneine-associated signals in mouse-lung cells with high Sps1 expression, a population enriched for AmB persisters. The Results also report significantly higher EGT1 expression in stationary-phase cells than in early-exponential-phase cells (Table S1), but do not establish that EGT1 was overexpressed in persisters from the mouse lungs. The claim conflates those populations and measurements. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe EGT gene, responsible for ergothioneine synthesis, plays a critical role in regulating AmB susceptibility.
“This provides insight into the critical role of the EGT gene, responsible for the synthesis of ergothioneine, in regulating AmB susceptibility [112].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [112]
The Results show that EGT1 is essential for ergothioneine production and that deleting it greatly reduces survival of stationary-phase cryptococcal cells under AmB treatment. The claim is broader than the finding: the Results report an unchanged AmB MIC, and the Discussion describes EGT1's role as specific to persistence rather than AmB resistance. (LLM, conf=0.87)
Experimental — accuracy not yet measuredReduced ATP synthesis due to limited respiration may be a key mechanism of AmB-tolerant Cryptococcus neoformans persister formation.
“A recent study has found that reduced ATP synthesis due to limited respiration may be a key mechanism of AmB-tolerant Cryptococcus neoformans persisters formation [3].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
Dormant cells have been observed in various cases of antifungal persistence, such as AmB-tolerant C. albicans biofilms and a mouse model of pulmonary cryptococcosis.
“Dormant cells have been observed in various cases of antifungal persistence, such as in AmB-tolerant C. albicans biofilms and in a mouse model of pulmonary cryptococcosis [3,33].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
Sertraline demonstrated satisfactory anti-persistence effect both in vitro and in vivo in a study of Cryptococcus persisters.
“In a study of Cryptococcus persisters, an antidepressant drug sertraline demonstrated satisfactory anti-persistence effect both in vitro and in vivo [3].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
Sps1 and ergothioneine can both reflect the level of Cryptococcus persistence, both in vitro and in vivo.
“In a recent research, Sps1(encoded by gene CNAG_00848, named stationary-phase specific indicator 1) detected by fluorescence-activated cell sorting and ergothioneine (provide protection in reactive oxygen species) evaluated by Raman spectroscopy can both reflect the level of Cryptococcus persistence, both in vitro and in vivo [3].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
Antifungal persistence has been observed in vivo in a few studies using animal models.
“Antifungal persistence has been observed in vivo in a few studies using animal models [3,39,48].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
AmB-tolerant persisters were found in a Cryptococcus pulmonary infection mouse model.
“and AmB-tolerant persisters were found in Cryptococcus pulmonary infection mouse model [3].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
Ergothioneine works synergically with glutathione to enhance tolerance to ROS, thereby supporting persistence in stationary-phase cells.
“Ergothioneine works synergically with glutathione to enhance tolerance to ROS, thereby supporting persistence in stationary-phase cells [3].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [3]
AmB-tolerant persisters are enriched in C. neoformans cells with high levels of Sps1 and ergothioneine.
“Ke et al. constructed a mouse model of pulmonary infection and demonstrated that AmB-tolerant persisters are enriched in C. neoformans cells with high levels of the stationary-phase protein Sps1 and the metabolic marker ergothioneine [112].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [112]
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
Part of this paper’s reference list could not be split into single entries.
Lewis, K. (2010) · Annual Review of Microbiology · doi:10.1146/annurev.micro.112408.134306 · Cited by 1,858 · see citing works
Distinguishing between resistance, tolerance and persistence to antibiotic treatment
Brauner, A., Fridman, O., Gefen, O., & Balaban, N. Q. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.34 · Cited by 1,612 · see citing works
Definitions and guidelines for research on antibiotic persistence
Balaban, N. Q., Helaine, S., Lewis, K., Ackermann, M., Aldridge, B., Andersson, D. I., Brynildsen, M. P., Bumann, D., Camilli, A., Collins, J. J., et al. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0196-3 · Cited by 1,313 · see citing works
Persistent bacterial infections and persister cells
Fisher, R. A., Gollan, B., & Helaine, S. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.42 · Cited by 1,243 · see citing works
Tackling the emerging threat of antifungal resistance to human health
Fisher, M. C., Alastruey-Izquierdo, A., Berman, J., Bicanic, T., Bignell, E. M., Bowyer, P., Bromley, M., Brüggemann, R., Garber, G., Cornely, O. A., et al. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00720-1 · Cited by 1,179 · see citing works
TREATMENT OF STAPHYLOCOCCAL INFECTIONS WITH PENICILLIN BY INTERMITTENT STERILISATION
Bigger, J. (1944) · The Lancet · doi:10.1016/s0140-6736(00)74210-3 · Cited by 1,164 · see citing works
Antibiotics induce redox-related physiological alterations as part of their lethality
Dwyer, D. J., Belenky, P. A., Yang, J. H., MacDonald, I. C., Martell, J. D., Takahashi, N. K., Chan, C. T. Y., Lobritz, M. A., Braff, D., Schwarz, E. G., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1401876111 · Cited by 938 · see citing works
Persister formation in Staphylococcus aureus is associated with ATP depletion
Conlon, B. P., Rowe, S. E., Gandt, A. B., Nuxoll, A. S., Donegan, N. P., Zalis, E. A., Clair, G., Adkins, J., Cheung, A. L., & Lewis, K. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.51 · Cited by 656 · see citing works
Drug resistance and tolerance in fungi.
Berman, J., & Krysan, D. J. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0322-2 · Cited by 654 · see citing works
Persistent bacterial infections: the interface of the pathogen and the host immune system
Monack, D. M., Mueller, A., & Falkow, S. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro955 · Cited by 574 · 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
<i>Candida albicans</i> Biofilms Produce Antifungal-Tolerant Persister Cells
LaFleur, M. D., Kumamoto, C. A., & Lewis, K. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00684-06 · Cited by 521 · see citing works
Microbiota-mediated colonization resistance: mechanisms and regulation
Caballero-Flores, G., Pickard, J. M., & Núñez, G. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00833-7 · Cited by 474 · see citing works
Systematic Genetic Analysis of Virulence in the Human Fungal Pathogen Cryptococcus neoformans
Liu, O. W., Chun, C. D., Chow, E. D., Chen, C., Madhani, H. D., & Noble, S. M. (2008) · Cell · doi:10.1016/j.cell.2008.07.046 · Cited by 443 · 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
Cavassin, F. B., Baú-Carneiro, J. L., Boas, R. R. V., & Queiroz‐Telles, F. (2021) · Infectious Diseases and Therapy · doi:10.1007/s40121-020-00382-7 · Cited by 390 · see citing works
Pu, Y., Li, Y., Jin, X., Tian, T., Ma, Q., Zhao, Z., Lin, S.-Y., Chen, Z., Li, B., Yao, G., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.10.022 · Cited by 387 · see citing works
Windels, E. M., Michiels, J. E., Fauvart, M., Wenseleers, T., den Bergh, B. V., & Michiels, J. J. (2019) · The ISME Journal · doi:10.1038/s41396-019-0344-9 · Cited by 366 · 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
Clinically relevant mutations in core metabolic genes confer antibiotic resistance
Lopatkin, A. J., Bening, S. C., Manson, A. L., Stokes, J. M., Kohanski, M. A., Badran, A. H., Earl, A. M., Cheney, N. J., Yang, J. H., & Collins, J. J. (2021) · Science · doi:10.1126/science.aba0862 · Cited by 357 · see citing works
Ergothioneine – a diet‐derived antioxidant with therapeutic potential
Halliwell, B., Cheah, I. K., & Tang, R. M. Y. (2018) · FEBS Letters · doi:10.1002/1873-3468.13123 · Cited by 305 · see citing works
Bacterial Persisters and Infection: Past, Present, and Progressing
Gollan, B., Grabe, G. J., Michaux, C., & Hélaine, S. (2019) · Annual Review of Microbiology · doi:10.1146/annurev-micro-020518-115650 · Cited by 274 · see citing works
Rosenberg, A., Ene, I. V., Bibi, M., Zakin, S., Segal, E. S., Ziv, N., Dahan, A. M., Colombo, A. L., Bennett, R. J., & Berman, J. (2018) · Nature Communications · doi:10.1038/s41467-018-04926-x · Cited by 270 · see citing works
Evolutionary causes and consequences of bacterial antibiotic persistence
Bakkeren, E., Diard, M., & Hardt, W. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0378-z · Cited by 226 · see citing works
Connolly, N. M. C., Theurey, P., Ádám‐Vizi, V., Bazan, N. G., Bernardi, P., Bolaños, J. P., Culmsee, C., Dawson, V. L., Deshmukh, M., Duchen, M. R., et al. (2017) · Cell Death and Differentiation · doi:10.1038/s41418-017-0020-4 · Cited by 208 · see citing works
Cryptococcus neoformans, a global threat to human health
Zhao, Y., Ye, L., Zhao, F., Zhang, L., Lu, Z., Chu, T., Wang, S., Liu, Z., Sun, Y., Chen, M., et al. (2023) · Infectious Diseases of Poverty · doi:10.1186/s40249-023-01073-4 · Cited by 206 · see citing works
Self-citationZhai, B., Wu, C., Wang, L., Sachs, M. S., & Lin, X. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00212-12 · Cited by 205 · see citing works
Self-citationFungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway
Belenky, P., Camacho, D., & Collins, J. J. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.12.021 · Cited by 199 · see citing works
Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda
Smith, K. D., Achan, B., Hullsiek, K. H., McDonald, T. R., Okagaki, L. H., Alhadab, A. A., Akampurira, A., Rhein, J., Meya, D. B., Boulware, D. R., et al. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01299-15 · Cited by 191 · see citing works
Lu, W., Chen, X., Wang, L., Li, H., & Fu, Y. V. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.9b04946 · Cited by 158 · see citing works
Self-citationProtozoan persister-like cells and drug treatment failure
Barrett, M. P., Kyle, D. E., Sibley, L. D., Radke, J. B., & Tarleton, R. L. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0238-x · Cited by 139 · see citing works
Fan, Y., & Lin, X. (2018) · Genetics · doi:10.1534/genetics.117.300656 · Cited by 136 · see citing works
Pluskal, T., Ueno, M., & Yanagida, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097774 · Cited by 128 · see citing works
Rhein, J., Hullsiek, K. H., Tugume, L., Nuwagira, E., Mpoza, E., Evans, E. E., Kiggundu, R., Pastick, K. A., Ssebambulidde, K., Akampurira, A., et al. (2019) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(19)30127-6 · Cited by 124 · see citing works
Fungal infections: Pathogenesis, antifungals and alternate treatment approaches
Reddy, G. K. K., Padmavathi, A. R., & Nancharaiah, Y. V. (2022) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2022.100137 · Cited by 124 · 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
Recent advances in laser tweezers Raman spectroscopy (LTRS) for label‐free analysis of single cells
Chan, J. W. (2012) · Journal of Biophotonics · doi:10.1002/jbio.201200143 · Cited by 105 · see citing works
Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine
van der Hoek, S. A., Darbani, B., Zugaj, K. E., Prabhala, B. K., Biron, M. B., Randelovic, M., Medina, J. B., Kell, D. B., & Borodina, I. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00262 · Cited by 102 · see citing works
Life 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 101 · see citing works
Protocol for quality control in metabolic profiling of biological fluids by U(H)PLC-MS
Gika, H., Zisi, C., Theodoridis, G. A., & Wilson, I. D. (2015) · Journal of Chromatography B · doi:10.1016/j.jchromb.2015.10.045 · Cited by 100 · see citing works
Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions
Cabral, D. J., Wurster, J. I., & Belenky, P. A. (2018) · Pharmaceuticals · doi:10.3390/ph11010014 · Cited by 99 · see citing works
A microbial transporter of the dietary antioxidant ergothioneine
Dumitrescu, D. G., Gordon, E. M., Kovalyova, Y., Seminara, A. B., Lowey, B., Forster, E. R., Zhou, W., Booth, C. J., Shen, A., Kranzusch, P. J., et al. (2022) · Cell · doi:10.1016/j.cell.2022.10.008 · Cited by 99 · see citing works
Overview of Treatment Approaches for Fungal Infections
Carmona, E. M., & LIMPER, A. H. (2017) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2017.04.003 · Cited by 86 · see citing works
Analysis of sphingolipids, sterols, and phospholipids in human pathogenic Cryptococcus strains
Singh, A., MacKenzie, A., Girnun, G. D., & Poeta, M. D. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m078600 · Cited by 85 · see citing works
Antibiotic persistence and tolerance: not just one and the same
Ronneau, S., Hill, P. W. S., & Hélaine, S. (2021) · Current Opinion in Microbiology · doi:10.1016/j.mib.2021.09.017 · Cited by 80 · see citing works
Structural basis of ergothioneine biosynthesis
Stampfli, A. R., Blankenfeldt, W., & Seebeck, F. P. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.04.002 · Cited by 79 · see citing works
Upadhya, R., Lam, W. C., Maybruck, B. T., Donlin, M. J., Chang, A. L., Kayode, S., Ormerod, K. L., Fraser, J. A., Doering, T. L., & Lodge, J. K. (2017) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2017.08.008 · Cited by 71 · see citing works
Klepser, M. E., Wolfe, E. J., & Pfaller, M. A. (1998) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/41.3.397 · Cited by 69 · see citing works
Hommel, B., Sturny-Leclère, A., Volant, S., Veluppillai, N., Duchateau, M., Yu, C.-H. A., Hourdel, V., Varet, H., Matondo, M., Perfect, J. R., et al. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007945 · Cited by 69 · see citing works
Davey, K. G., Holmes, A. D., Johnson, E. M., Székely, A., & Warnock, D. W. (1998) · Journal of Clinical Microbiology · doi:10.1128/jcm.36.4.926-930.1998 · Cited by 67 · see citing works
Superoxide-Mediated Protection of Escherichia coli from Antimicrobials
Mosel, M., Li, L., Drlica, K., & Zhao, X. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00754-13 · Cited by 61 · see citing works
Diagnosis and Management of Cryptococcal Relapse
Musubire, A. K. (2013) · Journal of AIDS & Clinical Research · doi:10.4172/2155-6113.s3-003 · Cited by 59 · see citing works
Cryptococcus neoformans sexual reproduction is controlled by a quorum sensing peptide
Tian, X., He, G., Hu, P., Chen, L., Tao, C., Cui, Y., Shen, L., Ke, W., Xu, H.-J., Zhao, Y., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0160-4 · Cited by 58 · see citing works
Self-citationArastehfar, A., Daneshnia, F., Cabrera, N., Penalva-Lopez, S., Sarathy, J., Zimmerman, M., Shor, E., & Perlin, D. S. (2023) · Nature Communications · doi:10.1038/s41467-023-36882-6 · Cited by 58 · see citing works
Self-citationHuo, W., Busch, L. M., Hernandez-Bird, J., Hamami, E., Marshall, C. W., Geisinger, E., Cooper, V. S., van Opijnen, T., Rosch, J. W., & Isberg, R. R. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01126-8 · Cited by 54 · see citing works
Cao, M., Liu, Y., Jiang, W., Meng, X., Zhang, W., Chen, W., Peng, D., & Xing, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-76650-w · Cited by 53 · see citing works
Fu, C., & Heitman, J. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1007113 · Cited by 52 · see citing works
Levinson, T., Dahan, A., Novikov, A., Paran, Y., Berman, J., & Ben‐Ami, R. (2021) · Mycoses · doi:10.1111/myc.13191 · Cited by 50 · see citing works
Wyk, M. V., Govender, N. P., Mitchell, T. G., & Litvintseva, A. P. (2014) · Journal of Clinical Microbiology · doi:10.1128/jcm.03177-13 · Cited by 48 · see citing works
Three-pathway combination for glutathione biosynthesis in Saccharomyces cerevisiae
Tang, L., Wang, W., Zhou, W., Cheng, K., Yang, Y., Liu, M., Cheng, K.-D., & Wang, S. (2015) · Microbial Cell Factories · doi:10.1186/s12934-015-0327-0 · Cited by 39 · see citing works
Sun, X., Wang, W., Wang, K., Yu, X., Liu, J., Zhou, F., Xie, B., & Li, S. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00127 · Cited by 37 · see citing works
Maxwell, M. J., Messer, S. A., Hollis, R. J., Diekema, D. J., & Pfaller, M. A. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.1.97-99.2003 · Cited by 35 · see citing works
Altamirano, S., Li, Z.-M., Fu, M., Ding, M., Fulton, S. R., Yoder, J., Tran, V., & Nielsen, K. (2021) · bioRxiv · doi:10.1128/mbio.02509-21 · Cited by 35 · see citing works
Persistence and drug tolerance in pathogenic yeast
Bojsen, R. K., Regenberg, B., & Folkesson, A. (2016) · Current Genetics · doi:10.1007/s00294-016-0613-3 · Cited by 33 · see citing works
Fornasaro, S., Gurian, E., Pagarin, S., Genova, E. C., Stocco, G., Decorti, G., Sergo, V., & Bonifacio, A. (2020) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2020.119024 · Cited by 33 · see citing works
Candida albicans amphotericin B-tolerant persister formation is closely related to surface adhesion
Sun, J., Li, Z., Chu, H., Guo, J., Jiang, G., & Qi, Q. (2016) · Mycopathologia · doi:10.1007/s11046-015-9894-1 · Cited by 32 · see citing works
Penicillin tolerance and treatment failure in group A streptococcal pharyngotonsillitis
van Asselt, G. J., Mouton, R. P., & van Boven, C. P. A. (1996) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/bf01591482 · Cited by 30 · see citing works
Ohkusu, M., Hata, K., & Takeo, K. (2001) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2001.tb09478.x · Cited by 30 · see citing works
Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial
Boulware, D. R., Nalintya, E., Rajasingham, R., Kirumira, P., Naluyima, R., Turya, F., Namanda, S., Rutakingirwa, M. K., Skipper, C. P., Nikweri, Y., et al. (2020) · Medical Mycology · doi:10.1093/mmy/myaa033 · Cited by 23 · see citing works
Monitoring Glycolysis and Respiration Highlights Metabolic Inflexibility of Cryptococcus neoformans
Lev, S., Li, C., Desmarini, D., Liuwantara, D., Sorrell, T. C., Hawthorne, W. J., & Djordjevic, J. T. (2020) · Pathogens · doi:10.3390/pathogens9090684 · Cited by 22 · see citing works
Hu, P., Ding, H., Shen, L., He, G., Liu, H., Tian, X., Tao, C., Bai, X., Liang, J., Jin, C., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009817 · Cited by 19 · see citing works
Self-citationCheon, S. A., Thak, E. J., Bahn, Y., & Kang, H. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-04290-8 · Cited by 15 · see citing works
Ababutain, I. M., & Alghamdi, A. I. (2021) · PeerJ · doi:10.7717/peerj.10561 · Cited by 14 · see citing works
Survey of amphotericin B susceptibility of Candida clinical isolates determined by Etest.
Chiu, Y.-S., Chang, S., Hsueh, P., Wang, J., Sun, H., & Chen, Y. (2006) · PubMed · Cited by 13 · see citing works
Self-citationWood, W. N., Mohler, K., Rinehart, J., & Ibba, M. (2021) · mBio · doi:10.1128/mbio.01132-21 · Cited by 13 · see citing works
Bahr, N. C., Skipper, C. P., Huppler-Hullsiek, K., Ssebambulidde, K., Morawski, B. M., Engen, N. W., Nuwagira, E., Quinn, C. M., Ramachandran, P., Evans, E. E., et al. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciac853 · Cited by 13 · see citing works
Genome-wide expression analyses of the stationary phase model of ageing in yeast
Wanichthanarak, K., Wongtosrad, N., & Petranović, D. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.05.008 · Cited by 12 · see citing works
Ke, W., Xie, Y., Hu, Y., Ding, H., Fan, X., Huang, J., Tian, X., Zhang, B., Xu, Y., Liu, X., et al. (2022) · mLife · doi:10.1002/mlf2.12011 · Cited by 11 · see citing works
Self-citationA cyclin protein governs the infectious and sexual life cycles of Cryptococcus neoformans
Hu, P., Liu, L., Ke, W., Tian, X., & Wang, L. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1697-3 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [26]26. Lin, X. ∙ Heitman, J. The biology of the Cryptococcus neoformans species complex Annu. Rev. Microbiol. 2006; 60:69-105 Crossref Scopus (322) PubMed Google Scholar
- [27]27. Zhao, Y. ∙ Lin, J. ∙ Fan, Y. ... Life cycle of Cryptococcus neoformans Annu. Rev. Microbiol. 2019; 73:17-42 Crossref Scopus (67) PubMed Google Scholar
Cited by
Sorted by citations
Monitoring kinetic processes of drugs and metabolites: Surface-enhanced Raman spectroscopy
Luo, Z., Chen, H., Bi, X., & Ye, J. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115483 · Cited by 34 · see citing works
New antifungal strategies and drug development against WHO critical priority fungal pathogens
Li, Y., Liu, Y., Jiang, Y., Yang, Y., Ni, W., Zhang, W., & Tan, L. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1662442 · Cited by 36 · see citing works
Self-citationPani, S., & Mohapatra, S. S. (2024) · Archives of Microbiology · doi:10.1007/s00203-024-04173-3 · Cited by 22 · see citing works
Antifungal resistance: Emerging mechanisms and implications (Review)
Kadariswantiningsih, I. N., Empitu, M. A., Santosa, T., & Alimu, Y. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13612 · Cited by 24 · see citing works
Recent progress in mushroom-derived ergothioneine: Techniques and applications
Weng, Y., Zhu, M., Ma, H., Hu, X., & Ren, L. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.105533 · Cited by 20 · see citing works
Yu, P., Zhou, M., Yu, D., Zhang, Z., Ye, S., Yu, Y., Sun, X., Li, S., & Hu, C. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.01.046 · Cited by 20 · see citing works
Pruitt, H. M., Zhu, J., Riley, S. P., & Shi, M. (2025) · Journal of Fungi · doi:10.3390/jof11030236 · Cited by 20 · see citing works
Is Cryptococcus neoformans a pleomorphic fungus?
Brown, J. C. S., & Ballou, E. R. (2024) · Current Opinion in Microbiology · doi:10.1016/j.mib.2024.102539 · Cited by 15 · 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
“Ke et al. constructed a mouse model of pulmonary infection and demonstrated that AmB-tolerant persisters are enriched in C. neoformans cells with high levels of the stationary-phase protein Sps1 and the metabolic marker ergothioneine [112].”
Briner, S. L., & Doering, T. L. (2025) · Current Biology · doi:10.1016/j.cub.2025.04.008 · Cited by 14 · see citing works
Overcoming Global Antifungal Challenges: Medical and Agricultural Aspects
Galgóczy, L. (2025) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.5c00103 · Cited by 13 · see citing works
Balancing act: thiol-based redox regulation drives fungal pathogenesis
Black, B., Kussat, T., & Kronstad, J. W. (2025) · Trends in Microbiology · doi:10.1016/j.tim.2025.06.003 · Cited by 10 · see citing works
Population heterogeneity in Cryptococcus neoformans: Impact on pathogenesis
Agrawal, R., de Castro, R. J. A., Sturny-Leclère, A., & Alanio, A. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012332 · Cited by 8 · see citing works
Persister cells in human fungal pathogens
Xie, Y., Ke, W., Wong, K. H., & Wang, L. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1013483 · Cited by 9 · see citing works
Self-citationAntifungal persistence: Clinical relevance and mechanisms
Wang, R., Lv, J., Chen, L., Zhao, Y., & Du, H. (2025) · PLoS pathogens · doi:10.1371/journal.ppat.1013456 · Cited by 12 · see citing works
“Ergothioneine works synergically with glutathione to enhance tolerance to ROS, thereby supporting persistence in stationary-phase cells [3].”
InfluentialSelf-citationZheng, L., Xu, Y., Wang, C., Dong, Y., & Guo, L. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1470454 · Cited by 7 · see citing works
Rocha, C. H. L., Rocha, F. M. G., Sanches, P. R., Rossi, A., & Martinez-Rossi, N. M. (2025) · Genes · doi:10.3390/genes16020146 · Cited by 5 · see citing works
Challenges posed by fungi to host immunity: Mechanisms of immune evasion
Gu, Y., Wang, H., Wang, Y.-S., Wang, L., & Jia, X.-M. (2026) · hLife · doi:10.1016/j.hlife.2025.12.008 · Cited by 5 · see citing works
Self-citationEmergence of traits in human fungal pathogens
Ma, X., Cui, J., Tao, Y., Liao, G., & Wang, L. (2026) · Trends in Microbiology · doi:10.1016/j.tim.2025.12.005 · Cited by 4 · see citing works
Self-citationAdvancing cryptococcal treatment: The role of nanoparticles in mitigating antifungal resistance
Lathakumari, R. H., Vajravelu, L. K., Satheesan, A., & Thulukanam, J. (2024) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2024.100323 · Cited by 4 · see citing works
Application of a One-Step method for rapid detection of nucleic acids from fungi
Yuan, J., Qiao, F., Chang, W., Yang, Y., Song, L., Liu, X., Tian, W., Ren, J., & Liu, X. (2025) · Mycology: An International Journal on Fungal Biology · doi:10.1080/21501203.2025.2471979 · Cited by 4 · see citing works
Zheng, L., Dong, Y., Wang, J., Jia, Y., Wang, W., Xu, Y., & Guo, L. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1519323 · Cited by 6 · see citing works
Exploring emerging drug responses in Cryptococcus
Liu, W., Gao, Y., & Ding, C. (2024) · Trends in Microbiology · doi:10.1016/j.tim.2024.07.002 · Cited by 3 · see citing works
Genetics and humoral responses of the immune system to Aspergillus fumigatus
Sanya, D. R. A., Jayachandran, K., & Onésime, D. (2025) · Molecular Immunology · doi:10.1016/j.molimm.2025.06.007 · Cited by 3 · see citing works
Günther, A., Burmester, A., Fabri, M., Tittelbach, J., & Wiegand, C. (2025) · Journal of Fungi · doi:10.3390/jof11100698 · Cited by 2 · see citing works
Wang, G., Feng, C., Ma, Z., Zhao, L., Yosri, M., Wang, Y., Gao, X., Zhu, W., Li, H., Song, H., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116658 · Cited by 2 · see citing works
Self-citationCytrynbaum, E. G., & McClean, M. N. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115740 · Cited by 1 · see citing works
Mechanisms of chronic infection: The multificated strategy of Cryptococcus
Qian, S., Fang, D., Fu, H., Wu, W., & Du, W. (2025) · Fungal Biology Reviews · doi:10.1016/j.fbr.2025.100469 · Cited by 1 · see citing works
Liu, X., Cui, C., Wang, P., Wang, H., Zhai, Y., Yang, Y., Chen, J., Liu, W., Dong, Z., Zhou, D., et al. (2026) · Veterinary Microbiology · doi:10.1016/j.vetmic.2026.110949 · Cited by 1 · see citing works
Self-citationHalliwell, B. B. (2026) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2026.101488 · Cited by 1 · see citing works
Research progress on responses and survival strategies of bacteria under oxidative stress
Yang, J., SUN, Y., Zhao, F., & Liao, H. (2026) · Microbial Pathogenesis · doi:10.1016/j.micpath.2026.108696 · Cited by 1 · see citing works
Joly‐Tonetti, N., Legouffe, R., Tomezyk, A., Gumez, C., Gaudin, M., Bonnel, D., & Schaller, M. (2024) · Infectious Diseases and Therapy · doi:10.1007/s40121-024-00979-2 · Cited by 1 · see citing works
CsdA-LaeB hub governs Aspergillus fumigatus virulence via FqC biosynthesisPreprint
Yin, W., Song, Z., Zhang, H., Ye, L., Lei, Y., Wang, L., Liu, X., Soto, N. M. M., Keller, N. P., Oakley, B. R., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6615529/v1
Self-citationFang, D., Su, B., Cheng, G., Wang, Q., Lan, K., Wang, H., Zhou, P., Bi, Y., Liu, C., Dou, D., et al. (2025) · 中国科学基金 · doi:10.3724/bnsfc-2024.12.15.0002
Self-citationBlack, B., Kussat, T., Lee, C. W. J., Qu, X., Hu, G., Caza, M., & Kronstad, J. W. (2025) · ACS Sensors · doi:10.1021/acssensors.5c01883
Two cases of refractory Cryptococcus gatti (C gatti) infection and literature review: Case report
Zeng, Y., Xiong, T., Xiang, W., Zhang, J., Li, L., Yuan, W., He, W., Deng, B., & Xu, H. (2026) · Medicine · doi:10.1097/md.0000000000046999
Bacterial persisters: from mechanism modules to target prioritization and inhibitor development
Chen, Z., Zhang, R., Dai, R., Zhou, Q., Pan, Y., & Huang, L. (2026) · Microbial Pathogenesis · doi:10.1016/j.micpath.2026.108472
Liu, J., Li, Z., Li, D., Liu, J., Su, Y., Leng, Y., Li, Y., Xu, L., Sun, L., Su, X., et al. (2026) · Drug Delivery · doi:10.1080/10717544.2026.2677305
Self-citationCong, L., Lin, Z., Li, Q., Wang, W., & Zhang, S. (2026) · mBio · doi:10.1128/mbio.00896-26
Prevalence and phenotypic features of voriconazole persistence in Aspergillus fumigatus
Li, X., Zhou, Z., Lin, H., Guo, J., Wu, W., Goldman, G. H., Lu, L., & Zhang, Y. (2026) · Mycology: An International Journal on Fungal Biology · doi:10.1080/21501203.2026.2679240
Pimenta, G. R., Gualque, M. W. D. L., Siqueto, M. J., Silva, S. D. M., Regasini, L. O., Mendes‐Giannini, M. J. S., & Fusco‐Almeida, A. M. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.00203-26
De novo lysine synthesis is required for the virulence of Cryptococcus neoformans
Feng, Y., Cui, J., Wang, M., Wang, W., Sun, J., & Liao, G. (2026) · Mycology: An International Journal on Fungal Biology · doi:10.1080/21501203.2026.2694879
Self-citationRepurposing FDA‐Approved Drugs to Inhibit Fungal PPTases for Broad‐Spectrum Synergy
Song, Z., Zhao, C., WANG, Q., Zhang, H., Liu, X., Wang, L., Bromley, M., & Yin, W. (2026) · Advanced Science · doi:10.1002/advs.77354
Self-citationThe common evolution of fungicide persistence in cryptococcosis patientsPreprint
Xie, Y., Ke, W., Fan, X., Xu, H., Wang, W., Zeng, Z., Zhang, N., Ma, H., Tang, Z., Zhu, H., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.26.747313
Self-citationTaş, E., Çetin, B., Yılmazer, A. N., & Işık, T. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12737-3
- Authors
- Ke, W., Xie, Y., Chen, Y., Ding, H., Ye, L., Qiu, H., Li, H., Zhang, L., Chen, L., Tian, X., Shen, Z., Song, Z., Fan, X., Zong, J.-F., Guo, Z., Ma, X., Xiao, M., Liao, G., Liu, C. H., Yin, W.-B., Dong, Z., Yang, F., Jiang, Y.-Y., Perlin, D. S., Chen, Y., Fu, Y. V., & Wang, L.
- Affiliations
- Chinese Academy of Sciences (CN)
- Tongji University (CN)
- Capital Medical University (CN)
- Southwest University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Hackensack Meridian Health (US)
- Corresponding author
- Fu, Yu V
- Wang, Linqi
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2024-02
- Volume
- 32
- Issue
- 2
- Pages
- 276-289.e7
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W4390753339
- Cited by
- 45
- References
- 79
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 9
- FWCI
- 13.65
- 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, 379 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
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Sciences
- Key Technologies Research and Development Program (2021YFC2300400, 2022YFC2303000, 2022YFC2303100)
- National Key Research and Development Program of China
- National Natural Science Foundation of China (32270206)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Cryptococcus neoformans, pulmonary cryptococcosis, fungicide tolerance, ergothioneine, sertraline, single-cell tracking, pulmonary infection, antifungal resistance
- MeSH terms
- Amphotericin B, Animals, Anti-Bacterial Agents, Antifungal Agents, Cryptococcosis, Cryptococcus neoformans, Fungicides, Industrial, Pneumonia, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
