Chapter 14 : Sensing Extracellular Signals in

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Sensing Extracellular Signals in , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap14-1.gif /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap14-2.gif


The chapter describes the abilities of to sense and adapt to a subset of environmental conditions it encounters. The mechanisms for sensing extracellular signals such as stress, light, nitrogen, carbon dioxide, and oxygen are emerging. There are several future paths toward understanding the light responses of . First, the functions of the opsin and phytochrome in light sensing, if any, are currently unknown. Second, the conformational effects of light on the white collar complex are also unknown in or in detail from any fungal system since the proteins are notoriously difficult to purify in abundance for structural and other studies. Third, the genes that are regulated by light remain to be fully elucidated, although this is being addressed through transcript profiling microarray and genetic screens, particularly since these genes should control ability to proliferate in the wild and cause disease in humans. The current model of the CO-sensing system in suggests that under limiting concentrations this molecule diffuses into the cell and is subsequently hydrated to HCO and fixed inside the cell by the CA Can2p. Analysis of deletion mutants identified two genes in addition to and that were required for full growth under hypoxic conditions. It is of interest to note that mutation of SRE1 and SCP1 leads to an increased sensitivity to ROS, which led Ingavale et al. to propose that there is a link in oxygen sensing between hypoxia, mitochondrial function, and ROS generation.

Citation: Idnurm A, Bahn Y, Shen W, Rutherford J, Mühlschlegel F. 2011. Sensing Extracellular Signals in , p 175-187. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch14

Key Concept Ranking

RNA Polymerase II
Fatty Acid Biosynthesis
DNA Repair Enzyme
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Stress-sensing pathways of . Extracellular stresses are sensed and the signal transmitted via signaling pathways. At present only a handful of regulators with overlapping functions are known that enter, or are predicted to enter, the nucleus to alter transcription.

Citation: Idnurm A, Bahn Y, Shen W, Rutherford J, Mühlschlegel F. 2011. Sensing Extracellular Signals in , p 175-187. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Light sensing is mediated by homologs of white collar 1 and 2 to control at least three responses in . Deletion of either the or gene renders insensitive to the inhibition of mating by light, increases UV sensitivity, and reduces virulence. (A) Strains of both mating types were cocultured in the light or dark for 2 days at room temperature on Murashige-Skoog medium. (B) Tenfold serial dilutions of wild-type and mutant strains were made on yeast extract peptone dextrose medium, and one set was irradiated with UV (100 J/m). Plates were incubated for 2 days at 30°C. (C) Ten mice were infected with strains, and survival was monitored over time. Data from Idnurm and Heitman ( ).

Citation: Idnurm A, Bahn Y, Shen W, Rutherford J, Mühlschlegel F. 2011. Sensing Extracellular Signals in , p 175-187. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Carbon dioxide sensing in . CO affects both capsule biosynthesis and mating. Carbon dioxide diffuses into the cell and is either spontaneously hydrated (elevated environmental concentrations of CO) to bicarbonate or alternatively enzymatically hydrated (low environmental concentrations of CO) by the action of the CA Can2. Bicarbonate stimulates the AC Cac1.

Citation: Idnurm A, Bahn Y, Shen W, Rutherford J, Mühlschlegel F. 2011. Sensing Extracellular Signals in , p 175-187. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

The fungal AC is a multidomain sensor. Serum, CO, and the quorum sensing molecules farnesol and 3-oxy-C12-homoserine lactone (3OC12HSL) influence AC activity in the fungal pathogen .

Citation: Idnurm A, Bahn Y, Shen W, Rutherford J, Mühlschlegel F. 2011. Sensing Extracellular Signals in , p 175-187. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch14
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abou-Gabal, M., and, M. Atia. 1978. Study of the role of pigeons in the dissemination of Cryptococcus neoformans in nature. Sabouraudia 16:6368.
2. Alspaugh, J. A.,, R. Pukkila-Worley,, T. Harashima,, L. M Cavallo,, D. Funnell,, G. M Cox,, J. R. Perfect,, J. W. Kronstad, and, J. Heitman. 2002. Adenylyl cyclase functions downstream of the Gα protein Gpa1 and controls mating and pathogenicity of Cryptococcus neoformans. Eukaryot. Cell 1:7584.
3. Bahn, Y.-S.,, G. M Cox,, J. R Perfect, and, J. Heitman. 2005. Carbonic anhydrase and CO2 sensing during Cryptococcus neoformans growth, differentiation, and virulence. Curr. Biol. 15:20132020.
4. Bahn, Y.-S., K. Kojima,, G. M Cox, and, J. Heitman. 2006. A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans. Mol. Biol. Cell 17:31223135.
5. Bahn, Y.-S., and, F. A Mühlschlegel. 2006. CO2 sensing in fungi and beyond. Curr. Opin. Microbiol. 9:572578.
6. Bahn, Y. S. 2008. Master and Commander in fungal pathogens: the two-component system and the HOG signaling pathway. Eukaryot. Cell 7:20172036.
7. Bahn, Y. S.,, S. GeunesBoyer, and, J. Heitman. 2007. Ssk2 mitogen-activated protein kinase kinase kinase governs divergent patterns of the stress-activated Hog1 signaling pathway in Cryptococcus neoformans. Eukaryot. Cell 6:22782289.
8. Bahn, Y. S.,, K. Kojima,, G. M Cox, and, J. Heitman. 2005. Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol. Biol. Cell 16:22852300.
9. Ballario, P.,, P. Vittorioso,, A. Magrelli,, C. Talora,, A. Cabibbo, and, G. Macino. 1996. White collar-1, a central regulator of blue light responses in Neurospora, is a zinc finger protein. EMBO J. 15:16501657.
10. Bava, A. J.,, R. Negroni, and, M. Bianchi. 1993. Cryptococcosis produced by a urease negative strain of Cryptococcus neoformans. J. Med. Vet. Mycol. 31:8789.
11. Beck, T., and, M. N Hall. 1999. The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402:689692.
12. Belden, W. J.,, L. F Larrondo,, A. C Froehlich,, M. Shi,, C. H Chen,, J. J. Loros, and, J. C Dunlap. 2007. The band mutation in Neurospora crassa is a dominant allele of ras-1 implicating RAS signaling in circadian output. Genes Dev. 21:14941505.
13. Bertram, P. G.,, J. H Choi,, J. Carvalho,, W. Ai,, C. Zeng,, T. F. Chan, and, X. F Zheng. 2000. Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases. J. Biol. Chem. 275:3572735733.
14. Biswas, K., and, J. Morschhäuser. 2005. The Mep2p ammonium permease controls nitrogen starvation-induced filamentous growth in Candida albicans. Mol. Microbiol. 56:649669.
15. Brown, S. M., L. T. Campbell, and, J. K Lodge. 2007. Cryptococcus neoformans, a fungus under stress. Curr. Opin. Microbiol. 10:320325.
16. Bryant, D. A., and, N.-U. Frigaard. 2006. Prokaryotic photosynthesis and phototrophy illuminated. Trends Microbiol. 14:488496.
17. Caparon, M. G.,, R. T Geist,, J. Perez-Casal, and, J. R Scott. 1992. Environmental regulation of virulence in group A streptococci: transcription of the gene encoding M protein is stimulated by carbon dioxide. J. Bacteriol. 174:56935701.
18. Cardenas, M. E.,, N. S Cutler,, M. C Lorenz,, C. J. Di Como, and, J. Heitman. 1999. The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev. 13:32713279.
19. Carter, R., and, M. M Nijhout. 1977. Control of gamete formation (exflagellation) in malaria parasites. Science 195:407409.
20. Chang, Y. C.,, C. M Bien,, H. Lee,, P. J. Espenshade, and, K. J KwonChung. 2007. Sre1p, a regulator of oxygen sensing and sterol homeostasis, is required for virulence in Cryptococcus neoformans. Mol. Microbiol. 64:614629.
21. Chun, C. D., O. W. Liu, and, H. D Madhani. 2007. A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans. PLoS Pathog. 3: e22.
22. Corrochano, L. M. 2007. Fungal photoreceptors: sensory molecules for fungal development and behaviour. Photochem. Photobiol. Sci. 6:725736.
23. Cox, G. M.,, T. S Harrison,, H. C McDade,, C. P Taborda,, G. Heinrich,, A. Casadevall, and, J. R Perfect. 2003. Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect. Immun. 71:173180.
24. Cox, G. M.,, J. Mukherjee,, G. T. Cole,, A. Casadevall, and, J. R Perfect. 2000. Urease as a virulence factor in experimental cryptococcosis. Infect. Immun. 68:443448.
25. Cutler, N. S.,, X. Pan,, J. Heitman, and, M. E Cardenas. 2001. The TOR signal transduction cascade controls cellular differentiation in response to nutrients. Mol. Biol. Cell 12:41034113.
26. Davis-Hanna, A.,, A. E Piispanen,, L. I. Stateva, and, D. A Hogan. 2008. Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis. Mol. Microbiol. 67:4762.
27. de Jesús-Berríos, M.,, L. Liu,, J. C Nussbaum,, G. M Cox,, J. S. Stamler, and, J. Heitman. 2003. Enzymes that counteract nitrosative stress promote fungal virulence. Curr. Biol. 13:19631968.
28. Eaton, K. A.,, C. L Brooks,, D. R Morgan, and, S. Krakowka. 1991. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 59:24702475.
29. Enserink, M. 2002. What mosquitoes want: secrets of host attraction. Science 298:9092.
30. Fang, H. M., and, Y. Wang. 2006. RA domain-mediated interaction of Cdc35 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development. Mol. Microbiol. 61:484496.
31. Fiskin, A. M., M. C. Zalles, and, R. G Garrison. 1990. Electron cytochemical studies of Cryptococcus neoformans grown on uric acid and related sources of nitrogen. J. Med. Vet. Mycol. 28:197207.
32. Fox, D. S.,, M. C Cruz,, R. A Sia,, H. Ke,, G. M Cox,, M. E. Cardenas, and, J. Heitman. 2001. Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12-FK506 in Cryptococcus neoformans. Mol. Microbiol. 39:835849.
33. Fox, D. S., and, J. Heitman. 2002. Good fungi gone bad: the corruption of calcineurin. Bioessays 24:894903.
34. Gerik, K. J.,, S. R Bhimireddy,, J. S Ryerse,, C. A. Specht, and, J. K Lodge. 2008. PKC1 is essential for protection against both oxidative and nitrosative stresses, cell integrity, and normal manifestation of virulence factors in the pathogenic fungus Cryptococcus neoformans. Eukaryot. Cell 7:16851698.
35. Ghosh, S.,, D. H Navarathna,, D. D Roberts,, J. T Cooper,, A. L Atkin,, T. M. Petro, and, K. W Nickerson. 2009. Arginine induced germ tube formation in Candida albicans is essential for escape from murine macrophage cell line RAW264.7. Infect. Immun. 77:15961605.
36. Giles, S. S., I. Batinic-Haberle, J. R. Perfect, and, G. M Cox. 2005. Cryptococcus neoformans mitochondrial superoxide dismutase: an essential link between antioxidant function and high-temperature growth. Eukaryot. Cell 4:4654.
37. Giles, S. S.,, J. E Stajich,, C. Nichols,, Q. D Gerrald,, J. A. Alspaugh,, F. Dietrich, and, J. R Perfect. 2006. The Cryptococcus neoformans catalase gene family and its role in antioxidant defense. Eukaryot. Cell 5:14471459.
38. Granger, D. L., J. R. Perfect, and, D. T Durack. 1985. Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide. J. Clin. Invest. 76:508516.
39. Guyton, A. C., and, J. E Hall. 2000. Textbook of Medical Physiology, 10th ed. W.B. Saunders, Philadelphia, PA.
40. Hall, R. A., F. Cottier, and, F. A Mühlschlegel. 2009. Molecular networks in the fungal pathogen Candida albicans. Adv. Appl. Microbiol. 67:191212.
41. Herrera-Estrella, A., and, B. A Horwitz. 2007. Looking through the eyes of fungi: molecular genetics of photoreception. Mol. Microbiol. 64:515.
42. Hetherington, A. M., and, J. A Raven. 2005. The biology of carbon dioxide. Curr. Biol. 15:R406–R410.
43. Heung, L. J.,, A. E Kaiser,, C. Luberto, and, M. Del Poeta. 2005. The role and mechanism of diacylglycerolprotein kinase C1 signaling in melanogenesis by Cryptococcus neoformans. J. Biol. Chem. 280:2854728555.
44. Heung, L. J.,, C. Luberto,, A. Plowden,, Y. A Hannun, and, M. Del Poeta. 2004. The sphingolipid pathway regulates Pkc1 through the formation of diacylglycerol in Cryptococcus neoformans. J. Biol. Chem. 279:2114421153.
45. Hohmann, S. 2002. Osmotic stress signaling and osmoadaptation in yeasts. Microbiol. Mol. Biol. Rev. 66:300372.
46. Hohmann, S., M. Krantz, and, B. Nordlander. 2007. Yeast osmoregulation. Methods Enzymol. 428:2945.
47. Hornby, J. M.,, E. C Jensen,, A. D Lisec,, J. J Tasto,, B. Jahnke,, R. Shoemaker,, P. Dussault, and, K. W Nickerson. 2001. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl. Environ. Microbiol. 67:29822992.
48. Huang, G.,, T. Srikantha,, N. Sahni,, S. Yi, and, D. R Soll. 2009. CO2 regulates white-to-opaque switching in Candida albicans. Curr. Biol. 19:330334.
49. Hubálek, Z. 1975. Distribution of Cryptococcus neoformans in a pigeon habitat. Folia Parasitol. 22:7379.
50. Hughes, A. L., B. L. Todd, and, P. J Espenshade. 2005. SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast. Cell 120:831842.
51. Idnurm, A., and, J. Heitman. 2005. Light controls growth and development via a conserved pathway in the fungal kingdom. PLoS Biol. 3:615626.
52. Ingavale, S. S.,, Y. C Chang,, H. Lee,, C. M. McClelland, M. L. Leong, and, K. J KwonChung. 2008. Importance of mitochondria in survival of Cryptococcus neoformans under low oxygen conditions and tolerance to cobalt chloride. PLoS Pathog. 4: e1000155.
53. Innocenti, A.,, R. A Hall,, C. Schlicker,, F. A. Mühlschlegel,, C. Steegborn, and, C. T Supuran. 2009. Carbonic anhydrase inhibitors. Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with aliphatic and aromatic carboxylates. Bioorg. Med. Chem. 17:26542657.
54. Innocenti, A.,, F. A Mühlschlegel,, R. A Hall,, C. Steegborn,, A. Scozzafava, and, C. T Supuran. 2008. Carbonic anhydrase inhibitors: inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus neoformans with simple anions. Bioorg. Med. Chem. Lett. 18:50665070.
55. Kamenetsky, M.,, S. Middelhaufe,, E. M Bank,, L. R Levin,, J. Buck, and, C. Steegborn. 2006. Molecular details of cAMP generation in mammalian cells: a tale of two systems. J. Mol. Biol. 362:623639.
56. Klengel, T., W.-J. Liang,, J. Chaloupka,, C. Ruoff,, K. Schröppel,, J. R Naglik,, S. E. Eckert,, E. G Mogensen,, K. Haynes,, M. F Tuite,, L. R. Levin,, J. Buck, and, F. A Mühlschlegel. 2005. Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr. Biol. 15:20212026.
57. Kojima, K.,, Y. S Bahn, and, J. Heitman. 2006. Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans. Microbiology 152:591604.
58. Kraus, P. R.,, D. S Fox,, G. M Cox, and, J. Heitman. 2003. The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function. Mol. Microbiol. 48:13771387.
59. Kraus, P. R., and, J. Heitman. 2003. Coping with stress: calmodulin and calcineurin in model and pathogenic fungi. Biochem. Biophys. Res. Commun. 311:11511157.
60. Kraus, P. R.,, C. B Nichols, and, J. Heitman. 2005. Calcium- and calcineurinindependent roles for calmodulin in Cryptococcus neoformans morphogenesis and hightemperature growth. Eukaryot. Cell 4:10791087.
61. Lee, H.,, C. M Bien,, A. L Hughes,, P. J Espenshade,, K. J. KwonChung, and, Y. C Chang. 2007. Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans. Mol. Microbiol. 65:10181033.
62. Levin, D. E. 2005. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 69:262291.
63. Liu, O. W.,, C. D Chun,, E. D Chow,, C. Chen,, H. D. Madhani, and, S. M Noble. 2008. Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell 135:174188.
64. Lu, Y.-K., K.-H. Sun, and, W.-C. Shen. 2005. Blue light negatively regulates the sexual filamentation via the Cwc1 and Cwc2 proteins in Cryptococcus neoformans. Mol. Microbiol. 56:280291.
65. Luberto, C.,, D. L Toffaletti,, E. A Wills,, S. C Tucker,, A. Casadevall,, J. R. Perfect,, Y. A. Hannun, and, M. Del Poeta. 2001. Roles for inositolphosphoryl ceramide synthase 1 (IPC1) in pathogenesis of C. neoformans. Genes Dev. 15:201212.
66. Makino, S.,, C. Sasakawa,, I. Uchida,, N. Terakado, and, M. Yoshikawa. 1988. Cloning and CO2-dependent expression of the genetic region for encapsulation from Bacillus anthracis. Mol. Microbiol. 2:371376.
67. Mandell, G. L.,, J. E Bennett, and, R. Dolin. 2000. Principles and Practice of Infectious Diseases. Churchill Livingstone, New York, NY.
68. Missall, T. A., J. F. Cherry-Harris, and, J. K Lodge. 2005. Two glutathione peroxidases in the fungal pathogen Cryptococcus neoformans are expressed in the presence of specific substrates. Microbiology 151:25732581.
69. Missall, T. A., and, J. K Lodge. 2005. Function of the thioredoxin proteins in Cryptococcus neoformans during stress or virulence and regulation by putative transcriptional modulators. Mol. Microbiol. 57:847858.
70. Missall, T. A., and, J. K Lodge. 2005. Thioredoxin reductase is essential for viability in the fungal pathogen Cryptococcus neoformans. Eukaryot. Cell 4:487489.
71. Missall, T. A., M. E. Pusateri, and, J. K Lodge. 2004. Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen, Cryptococcus neoformans. Mol. Microbiol. 51:14471458.
72. Mogensen, E. G.,, G. Janbon,, J. Chaloupka,, C. Steegborn,, M. S Fu,, F. Moyrand,, T. Klengel,, D. S Pearson,, M. A. Geeves,, J. Buck,, L. R. Levin, and, F. A Mühlschlegel. 2006. Cryptococcus neoformans senses CO 2through the carbonic anhydrase Can2 and the adenylyl cyclase Cac1. Eukaryot. Cell 5:103111.
73. Narasipura, S. D.,, J. G Ault,, M. J Behr,, V. Chaturvedi, and, S. Chaturvedi. 2003. Characterization of Cu, Zn superoxide dismutase (SOD1) gene knock-out mutant of Cryptococcus neoformans var. gattii: role in biology and virulence. Mol. Microbiol. 47:16811694.
74. Narasipura, S. D.,, V. Chaturvedi, and, S. Chaturvedi. 2005. Characterization of Cryptococcus neoformans variety gattii SOD2 reveals distinct roles of the two superoxide dismutases in fungal biology and virulence. Mol. Microbiol. 55:17821800.
75. Odom, A.,, M. Del Poeta,, J. Perfect, and, J. Heitman. 1997. The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein. Anti-microb. Agents Chemother. 41:156161.
76. Odom, A.,, S. Muir,, E. Lim,, D. L. Toffaletti,, J. Perfect, and, J. Heitman. 1997. Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J. 16:25762589.
77. Olszewski, M. A.,, M. C Noverr,, G.-H. Chen,, G. B Toews,, G. M. Cox,, J. R. Perfect, and, G. B Huffnagle. 2004. Urease expression by Cryptococcus neoformans promotes microvascular sequestration, thereby enhancing central nervous system invasion. Am. J. Pathol. 164:17611771.
78. Onyewu, C.,, J. R. Blankenship,, M. Del Poeta, and, J. Heitman. 2003. Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrob. Agents Chemother. 47:956964.
79. Polacheck, I., and, K. J KwonChung. 1980. Creatinine metabolism in Cryptococcus neoformans and Cryptococcus bacillisporus. J. Bacteriol. 142:1520.
80. Purschwitz, J.,, S. Müller,, C. Kastner, and, R. Fischer. 2006. Seeing the rainbow: light sensing in fungi. Curr. Opin. Microbiol. 9:566571.
81. Reilly, J. M., and, K. R Richards. 1993. Climate change damage and the trace gas index issue. Environ. Resource Econ. 3:4161.
82. Rhodes, J. C., and, G. D Roberts. 1975. Comparison of four methods for determining nitrate utilization by cryptococci. J. Clin. Microbiol. 1:910.
83. Ruane, P. J., L. J. Walker, and, W. L George. 1988. Disseminated infection caused by urease-negative Cryptococcus neoformans. J. Clin. Microbiol. 26:22242225.
84. Rutherford, J. C.,, X. Lin,, K. Nielsen, and, J. Heitman. 2008. Amt2 permease is required to induce ammoniumresponsive invasive growth and mating in Cryptococcus neoformans. Eukaryot. Cell 7:237246.
85. Sargent, M. L., W. R. Briggs, and, D. O Woodward. 1966. Circadian nature of a rhythm expressed by an invertaseless strain of Neurospora crassa. Plant Physiol. 41:13431349.
86. Sargent, M. L., and, S. H Kaltenborn. 1972. Effects of medium composition and carbon dioxide on circadian conidiation in Neurospora. Plant Physiol. 50:171175.
87. Schlicker, C.,, R. A Hall,, D. Vullo,, S. Middelhaufe,, M. Gertz,, C. T. Supuran,, F. A. Mühlschlegel, and, C. Steegborn. 2009. Structure and inhibition of the CO2-sensing carbonic anhydrase Can2 from the pathogenic fungus Cryptococcus neoformans. J. Mol. Biol. 385:12071220.
88. Shen, W.-C.,, R. C. Davidson,, G. M Cox, and, J. Heitman. 2002. Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans. Eukaryot. Cell 1:366377.
89. Sirard, J.-C., M. Mock, and, A. Fouet. 1994. The three Bacillus anthracis toxin genes are coordinately regulated by bicarbonate and temperature. J. Bacteriol. 176:51885192.
90. Slot, J. C., and, D. S Hibbett. 2007. Horizontal transfer of a nitrate assimilation gene cluster and ecological transitions in fungi: a phylogenetic study. PLoS ONE 2: e1097.
91. Smith, D. G.,, M. D Garcia-Pedrajas,, S. E Gold, and, M. H Perlin. 2003. Isolation and characterization from pathogenic fungi of genes encoding ammonium permeases and their roles in dimorphism. Mol. Microbiol. 50:259275.
92. Smith, R. S., and, B. H Iglewski. 2003. P. aeruginosa quorum-sensing systems and virulence. Curr. Opin. Microbiol. 6:5660.
93. Staib, F.,, S. K. Mishra,, T. Able, and, A. Blisse. 1976. Growth of Cryptococcus neoformans on uric acid agar. Zentralbl. Bakteriol. Orig. A 236:374385.
94. Steegborn, C.,, T. N Litvin,, L. R Levin,, J. Buck, and, H. Wu. 2005. Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment. Nat. Struct. Mol. Biol. 12:3237.
95. Supuran, C. T. 2008. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov. 7:168181.
96. Townsend, P. D.,, P. M Holliday,, S. Fenyk,, K. C Hess,, M. A. Gray,, D. R. Hodgson, and, M. J Cann. 2009. Stimulation of mammalian G-protein-responsive adenylyl cyclases by carbon dioxide. J. Biol. Chem. 284:784791.
97. Tremblay, P.-L., and, P. C Hallenbeck. 2009. Of blood, brains and bacteria, the Amt/Rh transporter family: emerging role of Amt as a unique microbial sensor. Mol. Microbiol. 71:1222.
98. Varma, A.,, S. Wu,, N. Guo,, W. Liao,, G. Lu,, A. Li,, Y. Hu,, G. Bulmer, and, K. J KwonChung. 2006. Identification of a novel gene, URE2, that functionally complements a ureasenegative clinical strain of Cryptococcus neoformans. Microbiology 152:37233731.
99. Wong, K. H., M. J. Hynes, and, M. A Davis. 2008. Recent advances in nitrogen regulation: a comparison between Saccharomyces cerevisiae and filamentous fungi. Eukaryot. Cell 7:917925.
100. Wormley, F. L.,, Jr., G. Heinrich,, J. L. Miller,, J. R Perfect, and, G. M Cox. 2005. Identification and characterization of an SKN7 homologue in Cryptococcus neoformans. Infect. Immun. 73:50225030.
101. Xu, X.-L.,, R. T. H. Lee,, H.-M. Fang,, Y.-M. Wang,, R. Li,, H. Zou,, Y. Zhu, and, Y. Wang. 2008. Bacterial peptidoglycan triggers Candida albicans hyphal growth by directly activating the adenylyl cyclase Cyr1p. Cell Host Microbe 4:2839.
102. Yeh, Y.-L.,, Y.-S. Lin,, B.-J. Su, and, W.-C. Shen. 2009. A screening for suppressor mutants reveals components involved in the blue lightinhibited sexual filamentation in Cryptococcus neoformans. Fungal Genet. Biol. 46:4254.
103. Zaragoza, O., and, A. Casadevall. 2004. Experimental modulation of capsule size in Cryptococcus neoformans. Biol. Proced. Online 6:1015.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error