Calcineurin is required for virulence of Cryptococcus neoformans

Odom, Audrey; Muir, Scott; Lim, Eric; Toffaletti, Dena L; Perfect, John; Heitman, Joseph

doi:10.1093/emboj/16.10.2576

Cited by 516Fungal Infections and StudiesSignaling Pathways in DiseaseAntifungal resistance and susceptibility

Calcineurin is required for virulence of Cryptococcus neoformans

Open access

Odom, Audrey, Muir, Scott, Lim, Eric, Toffaletti, Dena L, Perfect, John, Heitman, Joseph·1997·The EMBO Journal

DOI 10.1093/emboj/16.10.2576PMC PMC1169869

Open this paper in CoChat — free account Open PDF

Abstract

Cyclosporin A (CsA) and FK506 are antimicrobial, immunosuppressive natural products that inhibit signal transduction. In T cells and Saccharomyces cerevisiae, CsA and FK506 bind to the immunophilins cyclophilin A and FKBP12 and the resulting complexes inhibit the Ca2+-regulated protein phosphatase calcineurin. We find that growth of the opportunistic fungal pathogen Cryptococcus neoformans is sensitive to CsA and FK506 at 37 degrees C but not at 24 degrees C, suggesting that CsA and FK506 inhibit a protein required for C. neoformans growth at elevated temperature. Genetic evidence supports a model in which immunophilin-drug complexes inhibit calcineurin to prevent growth at 37 degrees C. The gene encoding the C. neoformans calcineurin A catalytic subunit was cloned and disrupted by homologous recombination. Calcineurin mutant strains are viable but do not survive in vitro conditions that mimic the host environment (elevated temperature, 5% CO2 or alkaline pH) and are no longer pathogenic in an animal model of cryptococcal meningitis. Introduction of the wild-type calcineurin A gene complemented these growth defects and restored virulence. Our findings demonstrate that calcineurin is required for C. neoformans virulence and may define signal transduction elements required for fungal pathogenesis that could be targets for therapeutic intervention.

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

Crossref · 10.1093/emboj/16.10.2576

Cites

80 of 80 references verified0 citation errors · 0 not checkable

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?

FK506, upon binding its intracellular receptor FKBP12, specifically inhibits calcineurin phosphatase activity-a mechanism conserved from yeast to humans and well-established in fungal pathogens.
“as FK506, upon binding its intracellular receptor FKBP12, specifically inhibits calcineurin phosphatase activity—a mechanism conserved from yeast to humans and well‐established in fungal pathogens [29].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [29]
The C. glabrata Δcnb1 strain phenotype (increased susceptibility to azoles and cell wall-damaging agents, decreased virulence) is consistent with previous findings for other pathogenic fungi.
“For example, the observed C. glabrata Δcnb1 strain phenotype, which is characterized by an increased susceptibility to azoles and cell wall-damaging agents as well as decreased virulence, is consistent with previous findings for other pathogenic fungi, such as C. albicans (2-4, 27), C. neoformans (11, 18, 21), and A. fumigatus (9, 30).”
From Roles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of Candida glabrata (2010) · cites this paper as [21]
In C. neoformans, calcineurin governs both morphogenesis during sexual reproduction and growth at host temperature.
“In C. neoformans, calcineurin governs both morphogenesis during sexual reproduction and growth at host temperature (Odom et al. 1997; Cruz et al. 2001).”
From Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence (2022) · cites this paper as Odom et al. 1997
Calcineurin is a bona fide client of Hsp90 and has been implicated in growth at high temperature and virulence of Cryptococcus.
“For example, calcineurin, a bona fide client of Hsp90, has been implicated in growth at high temperature as well as virulence of the pathogen [47–49].”
From Heat shock protein 90 localizes to the surface and augments virulence factors of Cryptococcus neoformans (2017) · cites this paper as [49]
The C. neoformans calcineurin catalytic subunit disruption strain was not viable in conditions mimicking the host environment (37°C, 5% CO2 or alkaline pH) and was avirulent.
“While the S. cerevisiae calcineurin catalytic subunit null mutant was able to grow at higher temperature (Liu et al., 1991), the C. neoformans calcineurin catalytic subunit disruption strain was not viable in conditions that mimicked the host environment (37° C, 5% CO2 or alkaline pH) and was avirulent (Odom et al., 1997).”
From Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis (2014) · cites this paper as Odom et al., 1997

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
Sikorski, R. S., & Hieter, P. (1989) · Genetics · doi:10.1093/genetics/122.1.19 · Cited by 8,685 · see citing works
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116 · see citing works
Getting started with yeast
Sherman, F. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)94004-v · Cited by 4,078 · see citing works
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension
Horton, R. M., Hunt, H. D., Ho, S. N., Pullen, J. K., & Pease, L. R. (1989) · Gene · doi:10.1016/0378-1119(89)90359-4 · Cited by 3,020 · see citing works
The mechanism of action of cyclosporin A and FK506
Schreiber, S. L., & Crabtree, G. R. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90111-j · Cited by 2,127 · cited 1× · see citing works
“CsA, FK506 and rapamycin are immunosuppressants Keywords: calcineurin/Cryptococcus neoformans/ that inhibit signal transduction processes required for cyclosporin A/FK506/virulence T-cell activation (reviewed in Heitman et al., 1992; Schreiber and Crabtree, 1992).”
A mammalian protein targeted by G1-arresting rapamycin–receptor complex
Brown, E. J., Albers, M. W., Bum Shin, T., ichikawa, K., Keith, C. T., Lane, W. S., & Schreiber, S. L. (1994) · Nature · doi:10.1038/369756a0 · Cited by 2,053 · see citing works
Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast
Heitman, J., Movva, N. R., & Hall, M. N. (1991) · Science · doi:10.1126/science.1715094 · Cited by 2,010 · see citing works
Self-citation
Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
Clipstone, N. A., & Crabtree, G. R. (1992) · Nature · doi:10.1038/357695a0 · Cited by 1,635 · see citing works
RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs
Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509 · see citing works
Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans
Mitchell, T. G., & Perfect, J. R. (1995) · Clinical Microbiology Reviews · doi:10.1128/cmr.8.4.515 · Cited by 1,213 · see citing works
Self-citation
Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells
Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.815 · Cited by 887 · see citing works
FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin
O’Keefe, S. J., Tamura, J., Kincaid, R. L., Tocci, M. J., & O’Neill, E. A. (1992) · Nature · doi:10.1038/357692a0 · Cited by 841 · see citing works
Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression
Kunz, J., Henríquez, R., Schneider, U., Deuter‐Reinhard, M., Movva, N. R., & Hall, M. N. (1993) · Cell · doi:10.1016/0092-8674(93)90144-f · Cited by 838 · see citing works
Overview of manual and automated DNA sequencing by the dideoxy chain termination method
CHEN, E., KUANG, W., & LEE, A. (1991) · Methods · doi:10.1016/s1046-2023(05)80158-6 · Cited by 834 · see citing works
NF-AT components define a family of transcription factors targeted in T-cell activation
Northrop, J. P., Ho, S. N., Chen, L., Thomas, D. J., Timmerman, L., Nolan, G. P., Admon, A., & Crabtree, G. R. (1994) · Nature · doi:10.1038/369497a0 · Cited by 573 · see citing works
Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA
Toffaletti, D. L., Rude, T. H., Johnston, S. A., Durack, D. T., & Perfect, J. R. (1993) · Journal of Bacteriology · doi:10.1128/jb.175.5.1405-1411.1993 · Cited by 488 · see citing works
Self-citation
Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases
Cunningham, K. W., & Fink, G. R. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.3.351 · Cited by 432 · see citing works
Calcineurin Inhibits VCX 1-Dependent H + /Ca 2 + Exchange and Induces Ca 2 + ATPases in Saccharomyces cerevisiae
Cunningham, K. W., & Fink, G. R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.5.2226 · Cited by 431 · see citing works
Complementation of a Capsule-Deficient Mutation of Cryptococcus neoformans Restores its Virulence
Chang, Y. C., & Kwon-Chung, K. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4912-4919.1994 · Cited by 427 · see citing works
TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast.
Helliwell, S. B., Wagner, P., Kunz, J., Deuter‐Reinhard, M., Henríquez, R., & Hall, M. N. (1994) · Molecular Biology of the Cell · doi:10.1091/mbc.5.1.105 · Cited by 390 · 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
The protein phosphatase calcineurin is essential for NaCl tolerance of Saccharomyces cerevisiae.
Mendoza, I., Rubio, F., Rodriguez-Navarro, A., & Pardo, J. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37038-2 · Cited by 350 · see citing works
Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans
Kwon-Chung, K. J., & Rhodes, J. C. (1986) · Infection and Immunity · doi:10.1128/iai.51.1.218-223.1986 · Cited by 345 · see citing works
Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice
Kwon-Chung, K. J., Polacheck, I., & Popkin, T. J. (1982) · Journal of Bacteriology · doi:10.1128/jb.150.3.1414-1421.1982 · Cited by 327 · see citing works
Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide.
Granger, D. L., Perfect, J. R., & Durack, D. T. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112000 · Cited by 308 · see citing works
Self-citation
FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae.
Heitman, J., Movva, N. R., HIESTAND, P. C., & Hall, M. N. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.5.1948 · Cited by 294 · see citing works
Self-citation
Yeast has homologs (CNA1 and CNA2 gene products) of mammalian calcineurin, a calmodulin-regulated phosphoprotein phosphatase
Cyert, M. S., Kunisawa, R., Kaim, D., & Thorner, J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7376 · Cited by 289 · see citing works
Chronic 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
Self-citation
Protein phosphatase type 2B (calcineurin)‐mediated, FK506‐sensitive regulation of intracellular ions in yeast is an important determinant for adaptation to high salt stress conditions.
Nakamura, T., Liu, Y., Hirata, D., Namba, H., Harada, S., Hirokawa, T., & Miyakawa, T. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06090.x · Cited by 270 · see citing works
The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin.
Dumont, F. J., Staruch, M. J., Koprak, S. L., Siekierka, J. J., Lin, C. S., Harrison, R., Sewell, T., Kindt, V. M., Beattie, T. R., & Wyvratt, M. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.3.751 · Cited by 250 · see citing works
Cryptococcosis in the era of AIDS 100 years after the discovery of Cryptococcus neoformans
Tomecki, K. J. (1997) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(97)80336-2 · Cited by 239 · see citing works
Temperature-dependent expression of virulence genes in Shigella species
Maurelli, A. T., Blackmon, B. P., & Curtiss, R. (1984) · Infection and Immunity · doi:10.1128/iai.43.1.195-201.1984 · Cited by 238 · see citing works
Identification of a chromosomal gene controlling temperature-regulated expression of Shigella virulence.
Maurelli, A. T., & Sansonetti, P. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.8.2820 · Cited by 238 · see citing works
Regulatory subunit (CNB1 gene product) of yeast Ca2+/calmodulin-dependent phosphoprotein phosphatases is required for adaptation to pheromone.
Cyert, M., & Thorner, J. W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.8.3460 · Cited by 236 · see citing works
Heat Shock Genes: Regulatory Role for Differentiation in Parasitic Protozoa
der Ploeg, L. H. T. V., Giannini, S. H., & Cantor, C. R. (1985) · Science · doi:10.1126/science.4012301 · Cited by 228 · see citing works
Sensitivity to cyclosporin A is mediated by cyclophilin in Neurospora crassa and Saccharomyces cerevisiae
Tropschug, M., Bartheimess, I. B., & Neupert, W. (1989) · Nature · doi:10.1038/342953a0 · Cited by 216 · see citing works
Calcineurin, the Ca2+/Calmodulin-Dependent Protein Phosphatase, Is Essential in Yeast Mutants with Cell Integrity Defects and in Mutants That Lack a Functional Vacuolar H+-Atpase
Garrett-Engele, P. W., Moilanen, B., & Cyert, M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4103 · Cited by 187 · see citing works
Genetic characterization of pathogenic Saccharomyces cerevisiae isolates.
McCusker, J. H., Clemons, K. V., Stevens, D. A., & Davis, R. W. (1994) · Genetics · doi:10.1093/genetics/136.4.1261 · Cited by 171 · see citing works
The plasmid‐encoded Yop2b protein of Yersinia pseudotuberculosis is a virulence determinant regulated by calcium and temperature at the level of transcription
Bölin, I., & Wolf‐Watz, H. (1988) · Molecular Microbiology · doi:10.1111/j.1365-2958.1988.tb00025.x · Cited by 171 · see citing works
Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans.
Lodge, J. K., Jackson-Machelski, E., Toffaletti, D. L., Perfect, J. R., & Gordon, J. I. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.25.12008 · Cited by 170 · see citing works
Self-citation
The α-Mating Type Locus of Cryptococcus neoformans Contains a Peptide Pheromone Gene
Moore, T. D. E., & Edman, J. C. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.3.1962-1970.1993 · Cited by 170 · see citing works
A calcineurin-like gene ppb1 + in fission yeast: mutant defects in cytokinesis, cell polarity, mating and spindle pole body positioning
Yoshida, T., Toda, T., & Yanagida, M. (1994) · Journal of Cell Science · doi:10.1242/jcs.107.7.1725 · Cited by 169 · see citing works
Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands.
Cardenas, M. E., Hemenway, C. S., Muir, R. S., Ye, R., Fiorentino, D. F., & Heitman, J. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06940.x · Cited by 160 · see citing works
Self-citation
The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein
John, A. R. O., Poeta, M. D., Perfect, J. R., & Heitman, J. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.1.156 · Cited by 153 · see citing works
Self-citation
Analysis of the preexisting and nuclear forms of nuclear factor of activated T cells.
Jain, J., Miner, Z., & Rao, A. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.2.837 · Cited by 145 · see citing works
The Product of HUM1, a Novel Yeast Gene, Is Required for Vacuolar Ca2+/H+ Exchange and Is Related to Mammalian Na+/Ca2+ Exchangers
Pozos, T. C., Seller, I., & Cyert, M. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3730 · Cited by 140 · see citing works
Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.
Breuder, T., Hemenway, C. S., Movva, N. R., Cardenas, M. E., & Heitman, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5372 · Cited by 135 · see citing works
Self-citation
The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid
Perfect, J. R., Toffaletti, D. L., & Rude, T. H. (1993) · Infection and Immunity · doi:10.1128/iai.61.10.4446-4451.1993 · Cited by 128 · see citing works
Self-citation
Targets of immunophilin‐immunosuppressant complexes are distinct highly conserved regions of calcineurin A.
Cardenas, M. E., Muir, R. S., Breuder, T., & Heitman, J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07277.x · Cited by 117 · see citing works
Self-citation
Saccharomyces cerevisiae virulence phenotype as determined with CD-1 mice is associated with the ability to grow at 42 degrees C and form pseudohyphae
McCusker, J. H., Clemons, K. V., Stevens, D. A., & Davis, R. W. (1994) · Infection and Immunity · doi:10.1128/iai.62.12.5447-5455.1994 · Cited by 116 · see citing works
The calmodulin‐dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene in Aspergillus nidulans.
Rasmussen, C. D., Garen, C. R., Brining, S. K., Kincaid, R. L., Means, R. L., & Means, A. R. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06544.x · Cited by 115 · see citing works
FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. II. Fermentation, isolation and physico-chemical and biological characteristics.
HATANAKA, H., KINO, T., Miyata, S., Inamura, N., KURODA, A., Goto, T., Tanaka, H., & OKUHARA, M. (1988) · The Journal of Antibiotics · doi:10.7164/antibiotics.41.1592 · Cited by 110 · see citing works
Analysis of expression and thermoregulation of the Yersinia pseudotuberculosis inv gene with hybrid proteins
Isberg, R. R., Swain, A., & Falkow, S. (1988) · Infection and Immunity · doi:10.1128/iai.56.8.2133-2138.1988 · Cited by 101 · see citing works
Stress tolerance and pathogenic potential of a mannitol mutant of Cryptococcus neoformans
Chaturvedi, V. P., Flynn, T., Niehaus, W. G., & Wong, B. (1996) · Microbiology · doi:10.1099/00221287-142-4-937 · Cited by 100 · see citing works
Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression.
Heitman, J., Movva, N. R., & Hall, M. N. (1992) · PubMed · Cited by 95 · see citing works
Self-citation
Isolation of Telomerelike Sequences from Cryptococcus neoformans and Their Use in High-Efficiency Transformation
Edman, J. C. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.6.2777-2783.1992 · Cited by 94 · see citing works
Temperature regulation of virulence genes in pathogenic bacteria: a general strategy for human pathogens?
Maurelli, A. T. (1989) · Microbial Pathogenesis · doi:10.1016/0882-4010(89)90106-x · Cited by 92 · see citing works
Cooperation of Calcineurin and Vacuolar H+-ATPase in Intracellular Ca2+Homeostasis of Yeast Cells
Tanida, I., Hasegawa, A., Iida, H., Ohya, Y., & Anraku, Y. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.17.10113 · Cited by 84 · see citing works
Regulatory Subunit (CNB1 Gene Product) of Yeast Ca2+/Calmodulin-Dependent Phosphoprotein Phosphatases Is Required for Adaptation to Pheromone
Cyert, M., & Thorner, J. W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.8.3460-3469.1992 · Cited by 82 · see citing works
Correlation between pathogenicity and temperature sensitivity in different strains of Histoplasma capsulatum.
Medoff, G., Maresca, B., Lambowitz, A. M., et al. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112757 · Cited by 79 · see citing works
Possible relationship of morphogenesis in pathogenic fungus, Histoplasma capsulatum, to heat shock response
Lambowitz, A. M., Kobayashi, G. S., Painter, A. A., et al. (1983) · Nature · doi:10.1038/303806a0 · Cited by 78 · see citing works
Cyclosporin A inhibits the growth of Cryptococcus neoformans in a murine model
Mody, C. H., Toews, G. B., & Lipscomb, M. F. (1988) · Infection and Immunity · doi:10.1128/iai.56.1.7-12.1988 · Cited by 69 · see citing works
Selection ofura5 andura3 mutants from the two varieties ofCryptococcus neoformanson 5-fluoroorotic acid medium
Kwon-Chung, K. J., Varma, A., Edman, J. C., & Bennett, J. E. (1992) · Medical Mycology · doi:10.1080/02681219280000081 · Cited by 66 · see citing works
vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly.
Hemenway, C. S., Dolinski, K. J., Cardenas, M. E., Hiller, M. A., Jones, E. W., & Heitman, J. (1995) · Genetics · doi:10.1093/genetics/141.3.833 · Cited by 62 · see citing works
Self-citation
Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant of Saccharomyces cerevisiae
Parent, S. A., NIELSEN, J. B. K., Morin, N. R., Chrebet, G. L., Ramadan, N., Dahl, A. M., Hsu, M. J., Bostian, K. A., & Foor, F. (1993) · Journal of General Microbiology · doi:10.1099/00221287-139-12-2973 · Cited by 62 · see citing works
Effects of cyclosporine in experimental cryptococcal meningitis
Perfect, J. R., & Durack, D. T. (1985) · Infection and Immunity · doi:10.1128/iai.50.1.22-26.1985 · Cited by 54 · see citing works
Self-citation
Improved calcineurin inhibition by yeast FKBP12-drug complexes. Crystallographic and functional analysis.
Rotonda, J., Burbaum, J. J., Chan, H., et al. (1993) · PubMed · doi:10.2210/pdb1yat/pdb · Cited by 53 · see citing works
Identification of regions on a 230-kilobase plasmid from enteroinvasive Escherichia coli that are required for entry into HEp-2 cells
Small, P., & Falkow, S. (1988) · Infection and Immunity · doi:10.1128/iai.56.1.225-229.1988 · Cited by 51 · see citing works
The actin gene fromCryptococcus neoformans: structure and phylogenetic analysis
Cox, G. M., Rude, T. H., Dykstra, C. C., & Perfect, J. R. (1995) · Medical Mycology · doi:10.1080/02681219580000521 · Cited by 51 · see citing works
Self-citation
The calmodulin‐dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene in Aspergillus nidulans.
Rasmussen, C. D., Garen, C. R., Brining, S. K., Kincaid, R. L., Means, R. L., & Means, A. R. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06703.x · Cited by 50 · see citing works
Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast.Preprint
Alarcón, C. M., Cardenas, M. E., & Heitman, J. (1996) · Genes & Development · doi:10.1101/gad.10.3.279 · Cited by 42 · see citing works
Self-citation
Cyclosporin A inhibits Coccidioides immitis in vitro and in vivo
Kirkland, T. N., & Fierer, J. (1983) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.24.6.921 · Cited by 38 · see citing works
Yeast as model T cells
Cardenas, M. E., Lorenz, M. C., Hemenway, C. S., & Heitman, J. (1994) · Perspectives in Drug Discovery and Design · doi:10.1007/bf02171739 · Cited by 34 · see citing works
Self-citation
Morphological transition in the human fungal pathogen Histoplasma capulatum
Maresca, B., Carratù, L., & Kobayashi, G. S. (1994) · Trends in Microbiology · doi:10.1016/0966-842x(94)90596-7 · Cited by 34 · see citing works
Identification of Immunosuppressive Drug Targets in Yeast
Heitman, J., Koller, A. A., Cardenas, M. E., & Hall, M. N. (1993) · Methods · doi:10.1006/meth.1993.1022 · Cited by 32 · see citing works
Self-citation
Regulation of Calcineurin Gene Expression in Schizosaccharomyces pombe
Plochocka-Zulinska, D., Rasmussen, G., & Rasmussen, C. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.24794 · Cited by 30 · see citing works
Cloning the Cryptococcus neoformans TRP1 gene by complementation in Saccharomyces cerevisiae
Perfect, J. R., Rude, T. H., Penning, L. M., et al. (1992) · Gene · doi:10.1016/0378-1119(92)90053-r · Cited by 27 · see citing works
Self-citation
Saccharomyces cerevisiae
Kelly, A. C., & Wickner, R. B. (2013) · Prion · doi:10.4161/pri.24845 · Cited by 27 · see citing works
Genetic complementation in Cryptococcus neoformans
Whelan, W. L., & Kwon-Chung, K. J. (1986) · Journal of Bacteriology · doi:10.1128/jb.166.3.924-929.1986 · Cited by 25 · see citing works
Adansonian study ofCandida albicans:intraspecific homogeneity exceptingC. stellatoideastrains
Kamiyama, A., Niimi, M., TOKUNAGA, M., & Nakayama, H. (1989) · Medical Mycology · doi:10.1080/02681218980000311 · Cited by 19 · see citing works

Flagged first, then by citations

Sorted by citations

Signal Transduction Cascades Regulating Fungal Development and Virulence
Lengeler, K. B., Davidson, R. C., D'souza, C., Harashima, T., Shen, W.-C., Wang, P., Pan, X., Waugh, M., & Heitman, J. (2000) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.64.4.746-785.2000 · Cited by 915 · see citing works
Self-citation
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 neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis
Kwon-Chung, K. J., Fraser, J. A., Doering, T. L., Wang, Z. A., Janbon, G., Idnurm, A., & Bahn, Y.-S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019760 · Cited by 531 · see citing works
Urease as a Virulence Factor in Experimental Cryptococcosis
Cox, G. M., Mukherjee, J., Cole, G. T., Casadevall, A., & Perfect, J. R. (2000) · Infection and Immunity · doi:10.1128/iai.68.2.443-448.2000 · Cited by 522 · see citing works
Self-citation
Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence
Sanglard, D., Ischer, F., Marchetti, O., Entenza, J., & Bille, J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03495.x · Cited by 350 · see citing works
Calcineurin is essential for survival during membrane stress in Candida albicans
Cruz, M. C., Goldstein, A. L., Blankenship, J. R., Del Poeta, M., Davis, D., Cardenas, M. E., Perfect, J. R., McCusker, J. H., & Heitman, J. (2002) · The EMBO Journal · doi:10.1093/emboj/21.4.546 · Cited by 342 · see citing works
Self-citation
What Makes Cryptococcus neoformans a Pathogen?
Buchanan, K. L., & Murphy, J. W. (1998) · Emerging Infectious Diseases · doi:10.3201/eid0401.980109 · Cited by 325 · see citing works
Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections.
Steinbach, W. J., Reedy, J. L., Cramer, R. A., Perfect, J. R., & Heitman, J. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1680 · Cited by 313 · see citing works
Fungal ß(1,3)-D-glucan synthesis
Douglas, C. M. (2001) · Medical Mycology · doi:10.1080/mmy.39.1.55.66 · Cited by 312 · see citing works
Antifungal Drugs: The Current Armamentarium and Development of New Agents
Robbins, N., Wright, G. D., & Cowen, L. E. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0002-2016 · Cited by 271 · see citing works
Our paths might cross: the role of the fungal cell wall integrity pathway in stress response and cross talk with other stress response pathways
Fuchs, B. B., & Mylonakis, E. (2009) · Eukaryotic Cell · doi:10.1128/ec.00193-09 · Cited by 266 · see citing works
Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus
Steinbach, W. J., Cramer, R. A., Perfect, B. Z., Asfaw, Y. G., Sauer, T. C., Najvar, L. K., Kirkpatrick, W. R., Patterson, T. F., Benjamin, D. K., Heitman, J., et al. (2006) · Eukaryotic Cell · doi:10.1128/ec.00139-06 · Cited by 264 · see citing works
Self-citation
Potent Synergism of the Combination of Fluconazole and Cyclosporine in Candida albicans
Marchetti, O., Moreillon, P., Glauser, M. P., Bille, J., & Sanglard, D. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.9.2373-2381.2000 · Cited by 252 · see citing works
CRZ1 , a target of the calcineurin pathway in Candida albicans
Karababa, M., Valentino, E., Pardini, G., Coste, A. T., Bille, J., & Sanglard, D. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.05037.x · Cited by 231 · see citing works
The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function
Kraus, P. R., Fox, D. S., Cox, G. M., & Heitman, J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03508.x · Cited by 217 · see citing works
Self-citation
Calcium-Calmodulin-Calcineurin Signaling: A Globally Conserved Virulence Cascade in Eukaryotic Microbial Pathogens
Park, H.-S., Lee, S. C., Cardenas, M. E., & Heitman, J. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.08.004 · Cited by 168 · see citing works
Self-citation
Laccase of Cryptococcus neoformans Is a Cell Wall-Associated Virulence Factor
Zhu, X., Gibbons, J., Garcia-Rivera, J., Casadevall, A., & Williamson, P. R. (2001) · Infection and Immunity · doi:10.1128/iai.69.9.5589-5596.2001 · Cited by 188 · see citing works
Calcineurin Is Essential for Candida albicans Survival in Serum and Virulence
Blankenship, J. R., Wormley, F. L., Boyce, M. K., Schell, W. A., Filler, S. G., Perfect, J. R., & Heitman, J. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.3.422-430.2003 · Cited by 186 · see citing works
Self-citation
Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12–FK506 in Cryptococcus neoformans
Fox, D. S., Cruz, M. C., Sia, R. A. L., Ke, H., Cox, G. M., Cardenas, M. E., & Heitman, J. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02295.x · Cited by 175 · see citing works
Self-citation
Calcineurin Target CrzA Regulates Conidial Germination, Hyphal Growth, and Pathogenesis of Aspergillus fumigatus
Cramer, R. A., Perfect, B. Z., Pinchai, N., Park, S., Perlin, D. S., Asfaw, Y. G., Heitman, J., Perfect, J. R., & Steinbach, W. J. (2008) · Eukaryotic Cell · doi:10.1128/ec.00086-08 · Cited by 172 · see citing works
Self-citation
FKBP Ligands—Where We Are and Where to Go?
Kolos, J. M., Voll, A. M., Bauder, M., & Hausch, F. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01425 · Cited by 158 · see citing works
Coping with stress: calmodulin and calcineurin in model and pathogenic fungi
Kraus, P. R., & Heitman, J. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01528-6 · Cited by 169 · see citing works
Self-citation
Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA
Soriani, F. M., Malavazi, I., Da Silva Ferreira, M. E., Savoldi, M., Von Zeska Kress, M. R., De Souza Goldman, M. H., Loss, O., Bignell, E., & Goldman, G. H. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06122.x · Cited by 168 · see citing works
Synergistic Antifungal Activities of Bafilomycin A 1 , Fluconazole, and the Pneumocandin MK-0991/Caspofungin Acetate (L-743,873) with Calcineurin Inhibitors FK506 and L-685,818 against Cryptococcus neoformans
Del Poeta, M., Cruz, M. C., Cardenas, M. E., Perfect, J. R., & Heitman, J. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.3.739-746.2000 · Cited by 169 · see citing works
Rapamycin and Less Immunosuppressive Analogs Are Toxic to Candida albicans and Cryptococcus neoformans via FKBP12-Dependent Inhibition of TOR
Cruz, M. C., Goldstein, A. L., Blankenship, J., Del Poeta, M., Perfect, J. R., McCusker, J. H., Bennani, Y. L., Cardenas, M. E., & Heitman, J. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.11.3162-3170.2001 · Cited by 159 · see citing works
Self-citation
Calcineurin is required for hyphal elongation during mating and haploid fruiting in Cryptococcus neoformans
Cruz, M. C., Fox, D. S., & Heitman, J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.5.1020 · Cited by 150 · see citing works
Self-citation
Good fungi gone bad: The corruption of calcineurin
Fox, D. S., & Heitman, J. (2002) · BioEssays · doi:10.1002/bies.10157 · Cited by 137 · see citing works
Self-citation
Risk Factors for Invasive Cryptococcus neoformans Diseases: A Case-Control Study
Lin, Y.-Y., Shiau, S., & Fang, C.-T. (2015) · PLOS ONE · doi:10.1371/journal.pone.0119090 · Cited by 128 · see citing works
Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis
Steen, B. R., Zuyderduyn, S., Toffaletti, D. L., Marra, M., Jones, S. J. M., Perfect, J. R., & Kronstad, J. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.6.1336-1349.2003 · Cited by 123 · see citing works
Self-citation
The Future of Antifungal Drug Therapy: Novel Compounds and Targets
Mota Fernandes, C., Dasilva, D., Haranahalli, K., McCarthy, J. B., Mallamo, J., Ojima, I., & Del Poeta, M. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01719-20 · Cited by 124 · see citing works
Calcineurin Is Essential for Virulence in Candida albicans
Bader, T., Bodendorfer, B., Schröppel, K., & Morschhäuser, J. (2003) · Infection and Immunity · doi:10.1128/iai.71.9.5344-5354.2003 · Cited by 121 · see citing works
Functional characterization of the Aspergillus fumigatus calcineurin
Ferreira, M. E. D. S., Heinekamp, T., Härtl, A., Brakhage, A. A., Semighini, C. P., Harris, S. D., Savoldi, M., de Gouvêa, P. F., Goldman, M. H. D. S., & Goldman, G. H. (2007) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2006.08.004 · Cited by 121 · see citing works
Role of Alternative Oxidase Gene in Pathogenesis of Cryptococcus neoformans
Akhter, S., McDade, H. C., Gorlach, J. M., Heinrich, G., Cox, G. M., & Perfect, J. R. (2003) · Infection and Immunity · doi:10.1128/iai.71.10.5794-5802.2003 · Cited by 115 · see citing works
Self-citation
Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis
Juvvadi, P. R., Lamoth, F., & Steinbach, W. J. (2014) · Fungal Biology Reviews · doi:10.1016/j.fbr.2014.02.004 · Cited by 116 · see citing works
Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis
Chen, Y.-L., Brand, A., Morrison, E. L., Silao, F. G. S., Bigol, U. G., Malbas, F. F., Nett, J. E., Andes, D. R., Solis, N. V., Filler, S. G., et al. (2011) · Eukaryotic Cell · doi:10.1128/ec.00310-10 · Cited by 107 · see citing works
Self-citation
Signal-transduction cascades as targets for therapeutic intervention by natural products
Cardenas, M. E., Sanfridson, A., Cutler, N. S., & Heitman, J. (1998) · Trends in Biotechnology · doi:10.1016/s0167-7799(98)01239-6 · Cited by 101 · see citing works
Self-citation
Convergent Evolution of Calcineurin Pathway Roles in Thermotolerance and Virulence inCandida glabrata
Chen, Y.-L., Konieczka, J. H., Springer, D. J., Bowen, S. E., Zhang, J., Silao, F. G. S., Bungay, A. A. C., Bigol, U. G., Nicolas, M. G., Abraham, S. N., et al. (2012) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.112.002279 · Cited by 97 · see citing works
Self-citation
Cryptococcus neoformans Histone Acetyltransferase Gcn5 Regulates Fungal Adaptation to the Host
O'Meara, T. R., Hay, C., Price, M. S., Giles, S., & Alspaugh, J. A. (2010) · Eukaryotic Cell · doi:10.1128/ec.00098-10 · Cited by 88 · see citing works
Roles of Calcineurin and Crz1 in Antifungal Susceptibility and Virulence of Candida glabrata
Miyazaki, T., Yamauchi, S., Inamine, T., Nagayoshi, Y., Saijo, T., Izumikawa, K., Seki, M., Kakeya, H., Yamamoto, Y., Yanagihara, K., et al. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01364-09 · 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
Localization and activity of the calcineurin catalytic and regulatory subunit complex at the septum is essential for hyphal elongation and proper septation in Aspergillus fumigatus
Juvvadi, P. R., Fortwendel, J. R., Rogg, L. E., Burns, K. A., Randell, S. H., & Steinbach, W. J. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07886.x · Cited by 80 · see citing works
Cch1 Mediates Calcium Entry in Cryptococcus neoformans and Is Essential in Low-Calcium Environments
Liu, M., Du, P., Heinrich, G., Cox, G. M., & Gelli, A. (2006) · Eukaryotic Cell · doi:10.1128/ec.00158-06 · Cited by 76 · see citing works
Antifungal Activity of Nonantifungal Drugs
Afeltra, J., & Verweij, P. E. (2003) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-003-0947-x · Cited by 63 · see citing works
Eca1, a Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase, Is Involved in Stress Tolerance and Virulence inCryptococcus neoformans
Fan, W., Idnurm, A., Breger, J., Mylonakis, E., & Heitman, J. (2007) · Infection and Immunity · doi:10.1128/iai.01977-06 · Cited by 57 · see citing works
Self-citation
Heat shock protein 90 localizes to the surface and augments virulence factors of Cryptococcus neoformans
Chatterjee, S., & Tatu, U. (2017) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0005836 · Cited by 57 · see citing works
Hsp90-dependent regulatory circuitry controlling temperature-dependent fungal development and virulence: Hsp90 and fungal development
O'Meara, T. R., & Cowen, L. E. (2014) · Cellular Microbiology · doi:10.1111/cmi.12266 · Cited by 48 · see citing works
Roles for Stress Response and Cell Wall Biosynthesis Pathways in Caspofungin Tolerance in Cryptococcus neoformans
Pianalto, K. M., Billmyre, R. B., Telzrow, C. L., & Alspaugh, J. A. (2019) · Genetics · doi:10.1534/genetics.119.302290 · Cited by 41 · see citing works
Calcineurin Localizes to the Hyphal Septum in Aspergillus fumigatus : Implications for Septum Formation and Conidiophore Development
Juvvadi, P. R., Fortwendel, J. R., Pinchai, N., Perfect, B. Z., Heitman, J., & Steinbach, W. J. (2008) · Eukaryotic Cell · doi:10.1128/ec.00200-08 · Cited by 42 · see citing works
Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence
Fu, C., Beattie, S. R., Jezewski, A. J., Robbins, N., Whitesell, L., Krysan, D. J., & Cowen, L. E. (2022) · Genetics · doi:10.1093/genetics/iyab164 · Cited by 31 · see citing works
The calcineurin pathway regulates extreme thermotolerance, cell membrane and wall integrity, antifungal resistance, and virulence in Candida auris
Cha, H., Won, D., Kang, S., Kim, E.-S., Lee, K.-A., Lee, W.-J., Lee, K.-T., & Bahn, Y.-S. (2025) · PLOS Pathogens · doi:10.1371/journal.ppat.1013363 · Cited by 24 · see citing works
Effects of CO2 in fungi
Chadwick, B. J., & Lin, X. (2024) · Current Opinion in Microbiology · doi:10.1016/j.mib.2024.102488 · Cited by 23 · see citing works
Calcineurin-dependent contributions to fitness in the opportunistic pathogen Candida glabrata
Pavesic, M. W., Gale, A. N., Nickels, T. J., Harrington, A. A., Bussey, M., & Cunningham, K. W. (2024) · mSphere · doi:10.1128/msphere.00554-23 · Cited by 22 · see citing works
Elongation Factor 3, EF3, Associates with the Calcium Channel Cch1 and Targets Cch1 to the Plasma Membrane inCryptococcus neoformans
Liu, M., & Gelli, A. (2008) · Eukaryotic Cell · doi:10.1128/ec.00116-08 · Cited by 15 · see citing works
GWT1encoding an inositol acyltransferase homolog is required for laccase repression and stress resistance in the basidiomyceteCryptococcus neoformans
Zhao, Q., Wei, D., Li, Z., Wang, Y., Zhu, X., & Zhu, X. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov086 · Cited by 8 · see citing works
Echinocandin tolerance and persistence in vitro are regulated by calcineurin signaling in Candida glabrata
Harrington, A. A., Nickels, T. J., & Cunningham, K. W. (2026) · mBio · doi:10.1128/mbio.02546-25 · Cited by 4 · see citing works
“Calcineurin signaling promotes virulence of C. glabrata (27, 28) , C. albicans (42, 50, 51), and other fungal pathogens (45, 52–54) in mouse models of systemic candidiasis.”
Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata
Su, Y., Li, Y., Xiao, M., Guo, D., Perlin, D. S., Shor, E., Xu, Y., & Li, Y. (2026) · Advanced Science · doi:10.1002/advs.76369 · Cited by 2 · see citing works

A yeast cyclophilin gene essential for lactate metabolism at high temperature.
Davis, E., Becker, A., Heitman, J., Hall, M. N., & Brennan, M. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.23.11169 · Cited by 68 · see citing works
Self-citation
Cyclophilin B is really a major growth factor in breast milk
Delmas, O. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101481
The N-Terminal Cyclophilin-Homologous Domain of a 150-Kilodalton Tumor Recognition Molecule Exhibits Both Peptidylprolyl cis-trans-Isomerase and Chaperone Activities
Rinfret, A., Collins, C., Ménard, R., et al. (1994) · Biochemistry · doi:10.1021/bi00173a008 · Cited by 52 · see citing works
Peptidyl Prolylcis/transIsomerases
Schiene‐Fischer, C. (2015) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0003020.pub2 · Cited by 4 · see citing works
Cyclophilins: The Structure and Functions of an Important Peptidyl-prolyl Isomerase
Idris, M. O., Idris, M., Fadahunsi, A. A., & Sedzro, D. M. (2019) · International Journal of Biochemistry Biophysics & Molecular Biology · doi:10.11648/j.ijbbmb.20190401.11 · Cited by 5 · see citing works

Authors: Odom, A., Muir, S., Lim, E., Toffaletti, D. L., Perfect, J., & Heitman, J.
Affiliations: Howard Hughes Medical Institute (US)
Duke Medical Center (US)
Corresponding author: Heitman, Joseph
ORCID: Perfect, John
Heitman, Joseph
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1997-05-15
Volume: 16
Issue: 10
Pages: 2576-2589
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1093/emboj/16.10.2576
PMC: PMC1169869
OpenAlex: W2162294247
Cited by: 516
References: 80
Citations by year: 2026: 15 · 2025: 14 · 2024: 15 · 2023: 11 · 2022: 16 · 2021: 9 · 2020: 22 · 2019: 14 · 2018: 13 · 2017: 21 · 2016: 22 · 2015: 14 · 2014: 36 · 2013: 17 · 2012: 11
FWCI: 15.92
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (AI28388)
Topics: Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords: calcineurin, Cryptococcus neoformans, fungal virulence, cyclosporine, FK506, immunophilins, FKBP12, temperature-dependent growth, opportunistic fungal pathogens, immunosuppression
MeSH terms: Amino Acid Sequence, Animals, Antifungal Agents, Base Sequence, Calmodulin-Binding Proteins, Cryptococcus neoformans, Drug Resistance, Microbial, Fungal Proteins, Genes, Fungal, Models, Genetic, Molecular Sequence Data, Phosphoprotein Phosphatases, Polyenes, Rabbits, Recombination, Genetic, Temperature, Virulence, Gene Expression Regulation, Fungal, Mutagenesis, Tacrolimus, Cyclosporine, Sequence Homology, Amino Acid, Calcineurin, Sirolimus

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

Calcineurin is required for virulence of Cryptococcus neoformans

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks