On the Roles of Calcineurin in Fungal Growth and Pathogenesis
详细信息 查看全文
- 作者：Ying-Lien Chen (1)
Lukasz Kozubowski (1)
Maria E. Cardenas (1)
Joseph Heitman (1) - 关键词：Fungi ; Virulence ; Fungal infections ; Antifungal agents ; Calcineurin inhibitor ; FK506 ; Cyclosporin A ; Treatment ; Candida albicans ; Cryptococcus neoformans ; Magnaporthe oryzae ; Ustilago maydis
- 刊名：Current Fungal Infection Reports
- 出版年：2010
- 出版时间：December 2010
- 年：2010
- 卷：4
- 期：4
- 页码：244-255
- 全文大小：374KB
- 参考文献：1. Klee CB, Crouch TH, Krinks MH: Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci USA 1979, 76:6270鈥?273. CrossRef
2. 鈥⑩€?Steinbach WJ, Reedy JL, Cramer RA Jr, et al.: Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat Rev Microbiol 2007, 5:418鈥?30. / This article reviews the roles of calcineurin pathways in the growth and virulence of three major human fungal pathogens, C. albicans, C. neoformans, and A. fumigatus. CrossRef
3. Crabtree GR, Schreiber SL: SnapShot: Ca2+-calcineurin-NFAT signaling. Cell 2009, 138:210. CrossRef
4. 鈥?Baek KH, Zaslavsky A, Lynch RC, et al.: Down鈥檚 syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature 2009, 459:1126鈥?130. / This article reports the discovery that an increased level of a CNI, Dscr1 (Down syndrome candidate region-1), in Down syndrome tissues markedly diminishes angiogenesis and constrains tumor formation. CrossRef
5. Aramburu J, Heitman J, Crabtree GR: Calcineurin: a central controller of signalling in eukaryotes. EMBO Rep 2004, 5:343鈥?48. CrossRef
6. Luan S: The CBL-CIPK network in plant calcium signaling. Trends Plant Sci 2009, 14:37鈥?2. CrossRef
7. Kumar R, Musiyenko A, Barik S: / Plasmodium falciparum calcineurin and its association with heat shock protein 90: mechanisms for the antimalarial activity of cyclosporin A and synergism with geldanamycin. Mol Biochem Parasitol 2005, 141:29鈥?7. CrossRef
8. Liu M, Du P, Heinrich G, et al.: Cch1 mediates calcium entry in / Cryptococcus neoformans and is essential in low-calcium environments. Eukaryot Cell 2006, 5:1788鈥?796. CrossRef
9. 鈥?Reedy JL, Filler SG, Heitman J: Elucidating the / Candida albicans calcineurin signaling cascade controlling stress response and virulence. Fungal Genet Biol 2009, 47:107鈥?16. / C. albicans calcineurin pathway components (Rcn1, Cch1, and Mid1) mediate aspects of calcineurin function, identifying them as elements of the calcineurin pathways. CrossRef
10. Stie J, Fox D: Calcineurin regulation in fungi and beyond. Eukaryot Cell 2008, 7:177鈥?86. CrossRef
11. Yokoyama H, Mizunuma M, Okamoto M, et al.: Involvement of calcineurin-dependent degradation of Yap1p in Ca2+-induced G2 cell-cycle regulation in / Saccharomyces cerevisiae. EMBO Rep 2006, 7:519鈥?24.
12. Heath VL, Shaw SL, Roy S, et al.: Hph1p and Hph2p, novel components of calcineurin-mediated stress responses in / Saccharomyces cerevisiae. Eukaryot Cell 2004, 3:695鈥?04. CrossRef
13. Bultynck G, Heath VL, Majeed AP, et al.: Slm1 and slm2 are novel substrates of the calcineurin phosphatase required for heat stress-induced endocytosis of the yeast uracil permease. Mol Cell Biol 2006, 26:4729鈥?745. CrossRef
14. Pozos TC, Sekler I, Cyert MS: The product of / HUM1, a novel yeast gene, is required for vacuolar Ca2+/H+ exchange and is related to mammalian Na+/Ca2+ exchangers. Mol Cell Biol 1996, 16:3730鈥?741.
15. Cybulski N, Hall MN: TOR complex 2: a signaling pathway of its own. Trends Biochem Sci 2009, 34:620鈥?27. CrossRef
16. Daquinag A, Fadri M, Jung SY, et al.: The yeast PH domain proteins Slm1 and Slm2 are targets of sphingolipid signaling during the response to heat stress. Mol Cell Biol 2007, 27:633鈥?50. CrossRef
17. Fadri M, Daquinag A, Wang S, et al.: The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell 2005, 16:1883鈥?900. CrossRef
18. Mulet JM, Martin DE, Loewith R, et al.: Mutual antagonism of target of rapamycin and calcineurin signaling. J Biol Chem 2006, 281:33000鈥?3007. CrossRef
19. Casamayor A, Torrance PD, Kobayashi T, et al.: Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Curr Biol 1999, 9:186鈥?97. CrossRef
20. Birchwood CJ, Saba JD, Dickson RC, et al.: Calcium influx and signaling in yeast stimulated by intracellular sphingosine 1-phosphate accumulation. J Biol Chem 2001, 276:11712鈥?1718. CrossRef
21. Zhao C, Jung US, Garrett-Engele P, et al.: Temperature-induced expression of yeast / FKS2 is under the dual control of protein kinase C and calcineurin. Mol Cell Biol 1998, 18:1013鈥?022.
22. Audhya A, Loewith R, Parsons AB, et al.: Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J 2004, 23:3747鈥?757. CrossRef
23. Aramburu J, Rao A, Klee CB: Calcineurin: from structure to function. Curr Top Cell Regul 2000, 36:237鈥?95. CrossRef
24. Boustany LM, Cyert MS: Calcineurin-dependent regulation of Crz1p nuclear export requires Msn5p and a conserved calcineurin docking site. Genes Dev 2002, 16:608鈥?19. CrossRef
25. 鈥?Egan JD, Garcia-Pedrajas MD, Andrews DL, et al.: Calcineurin is an antagonist to PKA protein phosphorylation required for postmating filamentation and virulence, while PP2A is required for viability in / Ustilago maydis. Mol Plant Microbe Interact 2009, 22:1293鈥?301. / This study reports that calcineurin (Ucn1) antagonizes PKA action, and deletion of the UCN1 gene causes dramatic multiple-budding phenotypes and attenuated virulence. CrossRef
26. Kraus PR, Fox DS, Cox GM, et al.: The / Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function. Mol Microbiol 2003, 48:1377鈥?387. CrossRef
27. Cyert MS, Kunisawa R, Kaim D, et al.: Yeast has homologs ( / CNA1 and / CNA2 gene products) of mammalian calcineurin, a calmodulin-regulated phosphoprotein phosphatase. Proc Natl Acad Sci U鈥塖鈥堿 1991, 88:7376鈥?380. CrossRef
28. Liu Y, Ishii S, Tokai M, et al.: The / Saccharomyces cerevisiae genes ( / CMP1 and / CMP2) encoding calmodulin-binding proteins homologous to the catalytic subunit of mammalian protein phosphatase 2B. Mol Gen Genet 1991, 227:52鈥?9. CrossRef
29. Ye RR, Bretscher A: Identification and molecular characterization of the calmodulin-binding subunit gene ( / CMP1) of protein phosphatase 2B from / Saccharomyces cerevisiae. An alpha-factor inducible gene. Eur J Biochem 1992, 204:713鈥?23. CrossRef
30. Matheos DP, Kingsbury TJ, Ahsan US, et al.: Tcn1p/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in / Saccharomyces cerevisiae. Genes Dev 1997, 11:3445鈥?458. CrossRef
31. Arron JR, Winslow MM, Polleri A, et al.: NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 2006, 441:595鈥?00. CrossRef
32. Beals CR, Sheridan CM, Turck CW, et al.: Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science 1997, 275:1930鈥?934. CrossRef
33. Hilioti Z, Gallagher DA, Low-Nam ST, et al.: GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs. Genes Dev 2004, 18:35鈥?7. CrossRef
34. Kozubowski L, Lee SC, Heitman J: Signalling pathways in the pathogenesis of / Cryptococcus. Cell Microbiol 2009, 11:370鈥?80. CrossRef
35. Braun BR, Johnson AD: Control of filament formation in / Candida albicans by the transcriptional repressor TUP1. Science 1997, 277:105鈥?09. CrossRef
36. Lo HJ, Kohler JR, DiDomenico B, et al.: Nonfilamentous / C. albicans mutants are avirulent. Cell 1997, 90:939鈥?49. CrossRef
37. Kwon-Chung KJ, Polacheck I, Popkin TJ: Melanin-lacking mutants of / Cryptococcus neoformans and their virulence for mice. J Bacteriol 1982, 150:1414鈥?421.
38. Cruz MC, Del Poeta M, Wang P, et al.: Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen / Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin. Antimicrob Agents Chemother 2000, 44:143鈥?49. CrossRef
39. Odom A, Del Poeta M, Perfect J, et al.: The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to / Cryptococcus neoformans by inhibition of a common target protein. Antimicrob Agents Chemother 1997, 41:156鈥?61.
40. 鈥⑩€?Singh SD, Robbins N, Zaas AK, et al.: Hsp90 governs echinocandin resistance in the pathogenic yeast / Candida albicans via calcineurin. PLoS Pathog 2009, 5:e1000532. / Hsp90 is found to physically interact with calcineurin and govern echinocandin resistance in C. albicans, and drug inhibitors of Hsp90 or calcineurin exhibit fungicidal activity in concert with echinocandins, providing a potential therapy for candidiasis. CrossRef
41. Onyewu C, Heitman J: Unique applications of novel antifungal drug combinations. Anti-infective Agents Med Chem 2007, 6:3鈥?5.
42. Morrell M, Fraser VJ, Kollef MH: Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 2005, 49:3640鈥?645. CrossRef
43. 鈥?Lockhart SR, Ahlquist AM, Iqbal N, et al.: Epidemiology and antifungal resistance results of current candidemia surveillance in Atlanta and Baltimore, US [abstract S3:2]. Presented at the 10th ASM Conference on / Candida and Candidiasis. Miami, FL, USA; March 22鈥?6, 2010. / C. albicans (35%鈥?9%), C. glabrata (27%), and C. parapsilosis (17%鈥?8%) are reported as major Candida species of candidemia, contributing to a case-fatality rate of 30% in Atlanta and 26% in Baltimore, in the United States.
44. Cruz MC, Goldstein AL, Blankenship JR, et al.: Calcineurin is essential for survival during membrane stress in / Candida albicans. EMBO J 2002, 21:546鈥?59. CrossRef
45. Bader T, Bodendorfer B, Schroppel K, et al.: Calcineurin is essential for virulence in / Candida albicans. Infect Immun 2003, 71:5344鈥?354. CrossRef
46. Bader T, Schroppel K, Bentink S, et al.: Role of calcineurin in stress resistance, morphogenesis, and virulence of a / Candida albicans wild-type strain. Infect Immun 2006, 74:4366鈥?369. CrossRef
47. Blankenship JR, Heitman J: Calcineurin is required for / Candida albicans to survive calcium stress in serum. Infect Immun 2005, 73:5767鈥?774. CrossRef
48. Blankenship JR, Wormley FL, Boyce MK, et al.: Calcineurin is essential for / Candida albicans survival in serum and virulence. Eukaryot Cell 2003, 2:422鈥?30. CrossRef
49. Sanglard D, Ischer F, Marchetti O, et al.: Calcineurin A of / Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. Mol Microbiol 2003, 48:959鈥?76. CrossRef
50. Onyewu C, Afshari NA, Heitman J: Calcineurin promotes infection of the cornea by / Candida albicans and can be targeted to enhance fluconazole therapy. Antimicrob Agents Chemother 2006, 50:3963鈥?965. CrossRef
51. Onyewu C, Wormley FL Jr, Perfect JR, et al.: The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of / Candida albicans. Infect Immun 2004, 72:7330鈥?333. CrossRef
52. Karababa M, Valentino E, Pardini G, et al.: CRZ1, a target of the calcineurin pathway in / Candida albicans. Mol Microbiol 2006, 59:1429鈥?451. CrossRef
53. Kullas AL, Martin SJ, Davis D: Adaptation to environmental pH: integrating the Rim101 and calcineurin signal transduction pathways. Mol Microbiol 2007, 66:858鈥?71. CrossRef
54. 鈥⑩€?Brand A, Shanks S, Duncan VM, et al.: Hyphal orientation of / Candida albicans is regulated by a calcium-dependent mechanism. Curr Biol 2007, 17:347鈥?52. / This article shows that C. albicans deploys calcium-dependent and Crz1-dependent mechanisms to control contact and voltage responses of hyphal orientation. CrossRef
55. Brand A, Gow NA: Mechanisms of hypha orientation of fungi. Curr Opin Microbiol 2009, 12:350鈥?57. CrossRef
56. Brand A, Lee K, Veses V, et al.: Calcium homeostasis is required for contact-dependent helical and sinusoidal tip growth in / Candida albicans hyphae. Mol Microbiol 2009, 71:1155鈥?164. CrossRef
57. Casadevall A, Perfect JR: / Cryptococcus neoformans. Washington, DC: ASM; 1998.
58. Byrnes EJ, Li W, Lewit Y, et al.: Emergence and pathogenicity of highly virulent / Cryptococcus gattii genotypes in the northwest United States. PLoS Pathog 2010, 6:e1000850. CrossRef
59. Fan W, Idnurm A, Breger J, et al.: Eca1, a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, is involved in stress tolerance and virulence in / Cryptococcus neoformans. Infect Immun 2007, 75:3394鈥?405. CrossRef
60. Odom A, Muir S, Lim E, et al.: Calcineurin is required for virulence of / Cryptococcus neoformans. EMBO J 1997, 16:2576鈥?589. CrossRef
61. Fox DS, Cruz MC, Sia RA, et al.: Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12-FK506 in / Cryptococcus neoformans. Mol Microbiol 2001, 39:835鈥?49. CrossRef
62. Kraus PR, Nichols CB, Heitman J: Calcium- and calcineurin-independent roles for calmodulin in / Cryptococcus neoformans morphogenesis and high-temperature growth. Eukaryot Cell 2005, 4:1079鈥?087. CrossRef
63. Garrett-Engele P, Moilanen B, Cyert MS: 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. Mol Cell Biol 1995, 15:4103鈥?114.
64. Hemenway CS, Dolinski K, Cardenas ME, et al.: / vph6 mutants of / Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly. Genetics 1995, 141:833鈥?44.
65. Mendoza I, Rubio F, Rodriguez-Navarro A, et al.: The protein phosphatase calcineurin is essential for NaCl tolerance of / Saccharomyces cerevisiae. J Biol Chem 1994, 269:8792鈥?796.
66. Fox DS, Cox GM, Heitman J: Phospholipid-binding protein Cts1 controls septation and functions coordinately with calcineurin in / Cryptococcus neoformans. Eukaryot Cell 2003, 2:1025鈥?035. CrossRef
67. Cruz MC, Fox DS, Heitman J: Calcineurin is required for hyphal elongation during mating and haploid fruiting in / Cryptococcus neoformans. EMBO J 2001, 20:1020鈥?032. CrossRef
68. Gorlach J, Fox DS, Cutler NS, et al.: Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in / Cryptococcus neoformans. EMBO J 2000, 19:3618鈥?629. CrossRef
69. Fox DS, Heitman J: Calcineurin-binding protein Cbp1 directs the specificity of calcineurin-dependent hyphal elongation during mating in / Cryptococcus neoformans. Eukaryot Cell 2005, 4:1526鈥?538. CrossRef
70. 鈥?Wilson RA, Talbot NJ: Under pressure: investigating the biology of plant infection by / Magnaporthe oryzae. Nat Rev Microbiol 2009, 7:185鈥?95. / This article reviews genetic control of appressorium formation during infection by the rice blast pathogen M. oryzae and documents that calcium channels are pivotal for invasive growth. CrossRef
71. Viaud MC, Balhadere PV, Talbot NJ: A / Magnaporthe grisea cyclophilin acts as a virulence determinant during plant infection. Plant Cell 2002, 14:917鈥?30. CrossRef
72. Lee SC, Lee YH: Calcium/calmodulin-dependent signaling for appressorium formation in the plant pathogenic fungus / Magnaporthe grisea. Mol Cells 1998, 8:698鈥?04.
73. Liu ZM, Kolattukudy PE: Early expression of the calmodulin gene, which precedes appressorium formation in / Magnaporthe grisea, is inhibited by self-inhibitors and requires surface attachment. J Bacteriol 1999, 181:3571鈥?577.
74. Choi JH, Kim Y, Lee YH: Functional analysis of / MCNA, a gene encoding a catalytic subunit of calcineurin, in the rice blast fungus / Magnaporthe oryzae. J Microbiol Biotechnol 2009, 19:11鈥?6.
75. 鈥?Choi J, Kim Y, Kim S, et al.: / MoCRZ1, a gene encoding a calcineurin-responsive transcription factor, regulates fungal growth and pathogenicity of / Magnaporthe oryzae. Fungal Genet Biol 2009, 46:243鈥?54. / This article demonstrates that Crz1 is a calcium-dependent downstream target of calcineurin that regulates transcription of cell-wall biosynthetic and ion machinery genes to evoke pathogenicity. CrossRef
76. Brefort T, Doehlemann G, Mendoza-Mendoza A, et al.: / Ustilago maydis as a pathogen. Annu Rev Phytopathol 2009, 47:423鈥?45. CrossRef
77. Gold S, Duncan G, Barrett K, et al.: cAMP regulates morphogenesis in the fungal pathogen / Ustilago maydis. Genes Dev 1994, 8:2805鈥?816. CrossRef
78. Chen YL, Montedonico AE, Kauffman S, et al.: Phosphatidylserine synthase and phosphatidylserine decarboxylase are essential for cell wall integrity and virulence in / Candida albicans. Mol Microbiol 2010, 75:1112鈥?132. CrossRef
79. 鈥?Campos CB, Di Benedette JP, Morais FV, et al.: Evidence for the role of calcineurin in morphogenesis and calcium homeostasis during mycelium-to-yeast dimorphism of / Paracoccidioides brasiliensis. Eukaryot Cell 2008, 7:1856鈥?864. / This article reports that in P. brasiliensis, a rare but fatal human fungal pathogen, calcineurin is required for the hyphae-to-yeast transition and promotes transcription of the CCH1 gene (encoding a P-type ATPase calcium channel). CrossRef
80. 鈥?Dannaoui E, Schwarz P, Lortholary O: In vitro interactions between antifungals and immunosuppressive drugs against zygomycetes. Antimicrob Agents Chemother 2009, 53:3549鈥?551. / Amphotericin B combined with cyclosporin A is found to exhibit synergistic fungicidal activity against Rhizopus oryzae, suggesting a potential therapy for mucormycosis. CrossRef
81. Santos M, de Larrinoa IF: Functional characterization of the / Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor. Curr Genet 2005, 48:88鈥?00. CrossRef
82. Miyazaki T, Yamauchi S, Inamine T, et al.: Roles of calcineurin and Crz1 in antifungal susceptibility and virulence of / Candida glabrata. Antimicrob Agents Chemother 2010, 54:1639鈥?643. CrossRef
83. Cruz MC, Sia RA, Olson M, et al.: Comparison of the roles of calcineurin in physiology and virulence in serotype D and serotype A strains of / Cryptococcus neoformans. Infect Immun 2000, 68:982鈥?85. CrossRef
84. Idnurm A, Walton FJ, Floyd A, et al.: Identification of / ENA1 as a virulence gene of the human pathogenic fungus / Cryptococcus neoformans through signature-tagged insertional mutagenesis. Eukaryot Cell 2009, 8:315鈥?26. CrossRef
85. da Silva Ferreira ME, Heinekamp T, Hartl A, et al.: Functional characterization of the / Aspergillus fumigatus calcineurin. Fungal Genet Biol 2007, 44:219鈥?30. CrossRef
86. Steinbach WJ, Cramer RA Jr, Perfect BZ, et al.: Calcineurin controls growth, morphology, and pathogenicity in / Aspergillus fumigatus. Eukaryot Cell 2006, 5:1091鈥?103. CrossRef
87. Cramer RA Jr, Perfect BZ, Pinchai N, et al.: Calcineurin target CrzA regulates conidial germination, hyphal growth, and pathogenesis of / Aspergillus fumigatus. Eukaryot Cell 2008, 7:1085鈥?097. CrossRef
88. Soriani FM, Malavazi I, da Silva Ferreira ME, et al.: Functional characterization of the / Aspergillus fumigatus CRZ1 homologue, CrzA. Mol Microbiol 2008, 67:1274鈥?291. CrossRef
89. Pinchai N, Perfect BZ, Juvvadi PR, et al.: / Aspergillus fumigatus calcipressin CbpA is involved in hyphal growth and calcium homeostasis. Eukaryot Cell 2009, 8:511鈥?19. CrossRef
90. Pinchai N, Juvvadi PR, Fortwendel JR, et al.: The / Aspergillus fumigatus P-type Golgi Ca2+/Mn2+-ATPase PmrA is involved in cation homeostasis and cell wall integrity but not essential for pathogenesis. Eukaryot Cell 2010, 9:472鈥?76. CrossRef
91. Harel A, Bercovich S, Yarden O: Calcineurin is required for sclerotial development and pathogenicity of / Sclerotinia sclerotiorum in an oxalic acid鈥搃ndependent manner. Mol Plant Microbe Interact 2006, 19:682鈥?93. CrossRef
92. Schumacher J, de Larrinoa IF, Tudzynski B: Calcineurin-responsive zinc finger transcription factor CRZ1 of / Botrytis cinerea is required for growth, development, and full virulence on bean plants. Eukaryot Cell 2008, 7:584鈥?01. CrossRef
93. Zhang H, Zhao Q, Liu K, et al.: / MgCRZ1, a transcription factor of / Magnaporthe grisea, controls growth, development and is involved in full virulence. FEMS Microbiol Lett 2009, 293:160鈥?69. CrossRef - 作者单位：Ying-Lien Chen (1)
Lukasz Kozubowski (1)
Maria E. Cardenas (1)
Joseph Heitman (1)
1. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, 27710, USA
文摘
Calcineurin is a calcium-activated phosphatase that controls morphogenesis and stress responses in eukaryotes. Fungal pathogens have adopted the calcineurin pathway to survive and effectively propagate within the host. The difficulty in treating fungal infections stems from similarities between pathogen and host eukaryotic cells. Using calcineurin inhibitors such as cyclosporin A or tacrolimus (FK506) in combination with antifungal drugs, including azoles or echinocandins, renders these drugs fungicidal, even towards drug-resistant species or strains, making calcineurin a promising drug target. This article summarizes the current understanding of the calcineurin pathway and its roles in governing the growth and virulence of pathogenic fungi, and compares and contrasts the roles of calcineurin in fungal pathogens that infect humans (Candida albicans and Cryptococcus neoformans) or plants (Magnaporthe oryzae and Ustilago maydis). Further investigation of calcineurin biology will advance opportunities to develop novel antifungal therapeutic approaches and provide insight into the evolution of virulence.