A functional link between hyphal maintenance and quorum sensing in Candida albicans

Molecular Microbiology

Volumn 103, Issue 4, 2017, Pages 595-617

  Polke, Melanie ^a   Sprenger, Marcel ^a   Scherlach, Kirstin ^a   Albán Proaño, María Cristina ^a,d   Martin, Ronny ^a   Hertweck, Christian ^a,b   Hube, Bernhard ^a,b,c   Jacobsen, Ilse D ^a,b,c  

^a HANS KNÖLL INSTITUTE   (Germany)

^b FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^c JENA UNIVERSITY HOSPITAL   (Germany)

^d HOSPITAL CARLOS ANDRADE MARÍN   (Ecuador)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; FARNESOL; RAS PROTEIN; CZF1 PROTEIN, CANDIDA ALBICANS; FUNGAL PROTEIN; TRANSCRIPTION FACTOR; VIRULENCE FACTOR;

ALLELE; ARTICLE; BIOACCUMULATION; CANDIDA ALBICANS; CELL DEATH; CELL LEVEL; CONTROLLED STUDY; CYTOLYSIS; CZF1 GENE; EED1 GENE; FUNGAL CELL; FUNGAL STRAIN; FUNGAL STRUCTURES; FUNGUS HYPHAE; GENE; GENE DELETION; NONHUMAN; NRG1 GENE; QUORUM SENSING; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; GENE EXPRESSION REGULATION; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PHYSIOLOGY;

CANDIDA ALBICANS; CYCLIC AMP; FARNESOL; FUNGAL PROTEINS; GENE EXPRESSION REGULATION, FUNGAL; HYPHAE; QUORUM SENSING; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; VIRULENCE FACTORS;

EID: 84991075514     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/mmi.13526     Document Type: Article

References (107)

1. Albuquerque, P., and Casadevall, A. (2012) Quorum sensing in fungi – a review. Med Mycol 50: 337–345.
2. Bahn, Y.S., Staab, J., and Sundstrom, P. (2003) Increased high-affinity phosphodiesterase PDE2 gene expression in germ tubes counteracts CAP1-dependent synthesis of cyclic AMP, limits hypha production and promotes virulence of Candida albicans. Mol Microbiol 50: 391–409.
3. Bahn, Y.S., and Sundstrom, P. (2001) CAP1, an adenylate cyclase-associated protein gene, regulates bud-hypha transitions, filamentous growth, and cyclic AMP levels and is required for virulence of Candida albicans. J Bacteriol 183: 3211–3223.
4. Bai, C., Xu, X.L., Wang, H.S., Wang, Y.M., Chan, F.Y., and Wang, Y. (2011) Characterization of a hyperactive Cyr1 mutant reveals new regulatory mechanisms for cellular cAMP levels in Candida albicans. Mol Microbiol 82: 879–893.
5. Banerjee, M., Thompson, D.S., Lazzell, A., Carlisle, P.L., Pierce, C., Monteagudo, C., et al. (2008) UME6, a novel filament-specific regulator of Candida albicans hyphal extension and virulence. Mol Biol Cell 19: 1354–1365.
6. Banerjee, M., Uppuluri, P., Zhao, X.R., Carlisle, P.L., Vipulanandan, G., Villar, C.C., et al. (2013) Expression of UME6, a key regulator of Candida albicans hyphal development, enhances biofilm formation via Hgc1- and Sun41-dependent mechanisms. Eukaryot Cell 12: 224–232.
7. Bendel, C.M., Hess, D.J., Garni, R.M., Henry-Stanley, M., and Wells, C.L. (2003) Comparative virulence of Candida albicans yeast and filamentous forms in orally and intravenously inoculated mice. Crit Care Med 31: 501–507.
8. Biswas, S., Van Dijck, P., and Datta, A. (2007) Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol Mol Biol Rev 71: 348–376.
9. Braun, B.R., and Johnson, A.D. (1997) Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 277: 105–109.
10. Brilhante, R.S., de Lima, R.A., Caetano, E.P., Leite, J.J., Castelo-Branco Dde, S., Ribeiro, J.F., et al. (2013) Effect of farnesol on growth, ergosterol biosynthesis, and cell permeability in Coccidioides posadasii. Antimicrob Agents Chemother 57: 2167–2170.
11. Brown, A.J., Budge, S., Kaloriti, D., Tillmann, A., Jacobsen, M.D., Yin, Z., et al. (2014) Stress adaptation in a pathogenic fungus. J Exp Biol 217: 144–155.
12. Brown, D.H., Jr, Giusani, A.D., Chen, X., and Kumamoto, C.A. (1999) Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene. Mol Microbiol 34: 651–662.
13. Calderone, R.A. (2002) Candida and Candidiasis. Washington, DC: ASM Press.
14. Cao, Y.Y., Cao, Y.B., Xu, Z., Ying, K., Li, Y., Xie, Y., et al. (2005) cDNA microarray analysis of differential gene expression in Candida albicans biofilm exposed to farnesol. Antimicrob Agents Chemother 49: 584–589.
15. Carlisle, P.L., and Kadosh, D. (2010) Candida albicans Ume6, a filament-specific transcriptional regulator, directs hyphal growth via a pathway involving Hgc1 cyclin-related protein. Eukaryot Cell 9: 1320–1328.
16. Chang, W., Li, Y., Zhang, L., Cheng, A., and Lou, H. (2012) Retigeric acid B attenuates the virulence of Candida albicans via inhibiting adenylyl cyclase activity targeted by enhanced farnesol production. PLoS One 7: e41624.
17. Cho, T., Aoyama, T., Toyoda, M., Nakayama, H., Chibana, H., and Kaminishi, H. (2007) Transcriptional changes in Candida albicans genes by both farnesol and high cell density at an early stage of morphogenesis in N-acetyl-d-glucosamine medium. Nihon Ishinkin Gakkai Zasshi 48: 159–167.
18. Davis-Hanna, A., Piispanen, A.E., Stateva, L.I., and Hogan, D.A. (2008) Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis. Mol Microbiol 67: 47–62.
19. Deveau, A., Piispanen, A.E., Jackson, A.A., and Hogan, D.A. (2010) Farnesol induces hydrogen peroxide resistance in Candida albicans yeast by inhibiting the Ras-cyclic AMP signaling pathway. Eukaryot Cell 9: 569–577.
20. Dumitru, R., Navarathna, D.H., Semighini, C.P., Elowsky, C.G., Dumitru, R.V., Dignard, D., et al. (2007) In vivo and in vitro anaerobic mating in Candida albicans. Eukaryot Cell 6: 465–472.
21. Enjalbert, B., and Whiteway, M. (2005) Release from quorum-sensing molecules triggers hyphal formation during Candida albicans resumption of growth. Eukaryot Cell 4: 1203–1210.
22. Feng, Q., Summers, E., Guo, B., and Fink, G. (1999) Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J Bacteriol 181: 6339–6346.
23. Funari, S.S., Prades, J., Escriba, P.V., and Barcelo, F. (2005) Farnesol and geranylgeraniol modulate the structural properties of phosphatidylethanolamine model membranes. Mol Membr Biol 22: 303–311.
24. Ganguly, S., Bishop, A.C., Xu, W., Ghosh, S., Nickerson, K.W., Lanni, F., et al. (2011) Zap1 control of cell-cell signaling in Candida albicans biofilms. Eukaryot Cell 10: 1448–1454.
25. Gola, S., Martin, R., Walther, A., Dunkler, A., and Wendland, J. (2003) New modules for PCR-based gene targeting in Candida albicans: rapid and efficient gene targeting using 100 bp of flanking homology region. Yeast 20: 1339–1347.
26. Grubb, S.E., Murdoch, C., Sudbery, P.E., Saville, S.P., Lopez-Ribot, J.L., and Thornhill, M.H. (2009) Adhesion of Candida albicans to endothelial cells under physiological conditions of flow. Infect Immun 77: 3872–3878.
27. Hall, R.A., Turner, K.J., Chaloupka, J., Cottier, F., De Sordi, L., Sanglard, D., et al. (2011) The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans. Eukaryot Cell 10: 1034–1042.
28. Han, T.L., Cannon, R.D., and Villas-Boas, S.G. (2011) The metabolic basis of Candida albicans morphogenesis and quorum sensing. Fungal Genet Biol 48: 747–763.
29. Harcus, D., Nantel, A., Marcil, A., Rigby, T., and Whiteway, M. (2004) Transcription profiling of cyclic AMP signaling in Candida albicans. Mol Biol Cell 15: 4490–4499.
30. Hazan, I., Sepulveda-Becerra, M., and Liu, H. (2002) Hyphal elongation is regulated independently of cell cycle in Candida albicans. Mol Biol Cell 13: 134–145.
31. Hogan, D.A., and Sundstrom, P. (2009) The Ras/cAMP/PKA signaling pathway and virulence in Candida albicans. Future Microbiol 4: 1263–1270.
32. Hogan, D.A., Vik, A., and Kolter, R. (2004) A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology. Mol Microbiol 54: 1212–1223.
33. Hornby, J.M., Jensen, E.C., Lisec, A.D., Tasto, J.J., Jahnke, B., Shoemaker, R., et al. (2001) Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl Environ Microbiol 67: 2982–2992.
34. Hornby, J.M., Kebaara, B.W., and Nickerson, K.W. (2003) Farnesol biosynthesis in Candida albicans: cellular response to sterol inhibition by zaragozic acid B. Antimicrob Agents Chemother 47: 2366–2369.
35. Hornby, J.M., and Nickerson, K.W. (2004) Enhanced production of farnesol by Candida albicans treated with four azoles. Antimicrob Agents Chemother 48: 2305–2307.
36. Inglis, D.O., and Sherlock, G. (2013) Ras signaling gets fine-tuned: regulation of multiple pathogenic traits of Candida albicans. Eukaryot Cell 12: 1316–1325.
37. Jabra-Rizk, M.A., Meiller, T.F., James, C.E., and Shirtliff, M.E. (2006a) Effect of farnesol on Staphylococcus aureus biofilm formation and antimicrobial susceptibility. Antimicrob Agents Chemother 50: 1463–1469.
38. Jabra-Rizk, M.A., Shirtliff, M., James, C., and Meiller, T. (2006b) Effect of farnesol on Candida dubliniensis biofilm formation and fluconazole resistance. FEMS Yeast Res 6: 1063–1073.
39. Jacobsen, I.D., Wilson, D., Wachtler, B., Brunke, S., Naglik, J.R., and Hube, B. (2012) Candida albicans dimorphism as a therapeutic target. Expert Rev Anti Infect Ther 10: 85–93.
40. Jung, W.H., Warn, P., Ragni, E., Popolo, L., Nunn, C.D., Turner, M.P., and Stateva, L. (2005) Deletion of PDE2, the gene encoding the high-affinity cAMP phosphodiesterase, results in changes of the cell wall and membrane in Candida albicans. Yeast 22: 285–294.
41. Kadosh, D., and Johnson, A.D. (2005) Induction of the Candida albicans filamentous growth program by relief of transcriptional repression: a genome-wide analysis. Mol Biol Cell 16: 2903–2912.
42. Kebaara, B.W., Langford, M.L., Navarathna, D.H., Dumitru, R., Nickerson, K.W., and Atkin, A.L. (2008) Candida albicans Tup1 is involved in farnesol-mediated inhibition of filamentous-growth induction. Eukaryot Cell 7: 980–987.
43. Kim, J., and Sudbery, P. (2011) Candida albicans, a major human fungal pathogen. J Microbiol 49: 171–177.
44. Krishnamurthy, S., Plaine, A., Albert, J., Prasad, T., Prasad, R., and Ernst, J.F. (2004) Dosage-dependent functions of fatty acid desaturase Ole1p in growth and morphogenesis of Candida albicans. Microbiology 150: 1991–2003.
45. Kruppa, M., Krom, B.P., Chauhan, N., Bambach, A.V., Cihlar, R.L., and Calderone, R.A. (2004) The two-component signal transduction protein Chk1p regulates quorum sensing in Candida albicans. Eukaryot Cell 3: 1062–1065.
46. Kumamoto, C.A., and Vinces, M.D. (2005) Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence. Cell Microbiol 7: 1546–1554.
47. Langford, M.L., Atkin, A.L., and Nickerson, K.W. (2009) Cellular interactions of farnesol, a quorum-sensing molecule produced by Candida albicans. Future Microbiol 4: 1353–1362.
48. Langford, M.L., Hargarten, J.C., Patefield, K.D., Marta, E., Blankenship, J.R., Fanning, S., et al. (2013) Candida albicans Czf1 and Efg1 coordinate the response to farnesol during quorum sensing, white-opaque thermal dimorphism, and cell death. Eukaryot Cell 12: 1281–1292.
49. Langford, M.L., Hasim, S., Nickerson, K.W., and Atkin, A.L. (2010) Activity and toxicity of farnesol towards Candida albicans are dependent on growth conditions. Antimicrob Agents Chemother 54: 940–942.
50. Lindsay, A.K., Deveau, A., Piispanen, A.E., and Hogan, D.A. (2012) Farnesol and cyclic AMP signaling effects on the hypha-to-yeast transition in Candida albicans. Eukaryot Cell 11: 1219–1225.
51. Loeb, J.D., Sepulveda-Becerra, M., Hazan, I., and Liu, H. (1999) A G1 cyclin is necessary for maintenance of filamentous growth in Candida albicans. Mol Cell Biol 19: 4019–4027.
52. Lu, Y., Su, C., and Liu, H. (2014a) Candida albicans hyphal initiation and elongation. Trends Microbiol 22: 707–714.
53. Lu, Y., Su, C., Unoje, O., and Liu, H. (2014b) Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation. Proc Natl Acad Sci U S A 111: 1975–1980.
54. Martin, R., Moran, G.P., Jacobsen, I.D., Heyken, A., Domey, J., Sullivan, D.J., et al. (2011a) The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension. PLoS One 6: e18394.
55. Martin, R., Wachtler, B., Schaller, M., Wilson, D., and Hube, B. (2011b) Host-pathogen interactions and virulence-associated genes during Candida albicans oral infections. Int J Med Microbiol 301: 417–422.
56. Martins, M., Henriques, M., Azeredo, J., Rocha, S.M., Coimbra, M.A., and Oliveira, R. (2007) Morphogenesis control in Candida albicans and Candida dubliniensis through signaling molecules produced by planktonic and biofilm cells. Eukaryot Cell 6: 2429–2436.
57. Mosel, D.D., Dumitru, R., Hornby, J.M., Atkin, A.L., and Nickerson, K.W. (2005) Farnesol concentrations required to block germ tube formation in Candida albicans in the presence and absence of serum. Appl Environ Microbiol 71: 4938–4940.
58. Moyes, D.L., Wilson, D., Richardson, J.P., Mogavero, S., Tang, S.X., Wernecke, J., et al. (2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532: 64–68.
59. Mukhopadhyay, K., Prasad, T., Saini, P., Pucadyil, T.J., Chattopadhyay, A., and Prasad, R. (2004) Membrane sphingolipid–ergosterol interactions are important determinants of multidrug resistance in Candida albicans. Antimicrob Agents Chemother 48: 1778–1787.
60. Murad, A.M., Leng, P., Straffon, M., Wishart, J., Macaskill, S., MacCallum, D., et al. (2001) NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J 20: 4742–4752.
61. Navarathna, D.H., Hornby, J.M., Hoerrmann, N., Parkhurst, A.M., Duhamel, G.E., and Nickerson, K.W. (2005) Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis. J Antimicrob Chemother 56: 1156–1159.
62. Navarathna, D.H., Hornby, J.M., Krishnan, N., Parkhurst, A., Duhamel, G.E., and Nickerson, K.W. (2007) Effect of farnesol on a mouse model of systemic candidiasis, determined by use of a DPP3 knockout mutant of Candida albicans. Infect Immun 75: 1609–1618.
63. Nickerson, K., Atkin, A., Hargarten, J., Pathirana, R., and Hasim, S. (2012) Thoughts on quorum sensing and fungal dimorphism. In Biocommunication of Fungi. Witzany G. (ed). Dordrecht: Springer Netherlands, pp. 189–204.
64. Nickerson, K.W., Atkin, A.L., and Hornby, J.M. (2006) Quorum sensing in dimorphic fungi: farnesol and beyond. Appl Environ Microbiol 72: 3805–3813.
65. Noble, S.M., French, S., Kohn, L.A., Chen, V., and Johnson, A.D. (2010) Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat Genet 42: 590–598.
66. Odds, F.C. (1987) Candida infections: an overview. Crit Rev Microbiol 15: 1–5.
67. Oh, K.B., Miyazawa, H., Naito, T., and Matsuoka, H. (2001) Purification and characterization of an autoregulatory substance capable of regulating the morphological transition in Candida albicans. Proc Natl Acad Sci U S A 98: 4664–4668.
68. O'Meara, T.R., Veri, A.O., Ketela, T., Jiang, B., Roemer, T., and Cowen, L.E. (2015) Global analysis of fungal morphology exposes mechanisms of host cell escape. Nat Commun 6: 6741.
69. Park, H.O., and Bi, E. (2007) Central roles of small GTPases in the development of cell polarity in yeast and beyond. Microbiol Mol Biol Rev 71: 48–96.
70. Phillips, A.J., Crowe, J.D., and Ramsdale, M. (2006) Ras pathway signaling accelerates programmed cell death in the pathogenic fungus Candida albicans. Proc Natl Acad Sci U S A 103: 726–731.
71. Piispanen, A.E., Bonnefoi, O., Carden, S., Deveau, A., Bassilana, M., and Hogan, D.A. (2011) Roles of Ras1 membrane localization during Candida albicans hyphal growth and farnesol response. Eukaryot Cell 10: 1473–1484.
72. Piispanen, A.E., Grahl, N., Hollomon, J.M., and Hogan, D.A. (2013) Regulated proteolysis of Candida albicans Ras1 is involved in morphogenesis and quorum sensing regulation. Mol Microbiol 89: 166–178.
73. Ramage, G., Saville, S.P., Wickes, B.L., and Lopez-Ribot, J.L. (2002) Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Appl Environ Microbiol 68: 5459–5463.
74. Reuss, O., Vik, A., Kolter, R., and Morschhauser, J. (2004) The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341: 119–127.
75. Roman, E., Alonso-Monge, R., Gong, Q., Li, D., Calderone, R., and Pla, J. (2009) The Cek1 MAPK is a short-lived protein regulated by quorum sensing in the fungal pathogen Candida albicans. FEMS Yeast Res 9: 942–955.
76. Sabra, A., Bessoule, J.J., Atanasova-Penichon, V., Noel, T., and Dementhon, K. (2014) Host–pathogen interaction and signaling molecule secretion are modified in the dpp3 knockout mutant of Candida lusitaniae. Infect Immun 82: 413–422.
77. Sasse, C., Schillig, R., Dierolf, F., Weyler, M., Schneider, S., Mogavero, S., et al. (2011) The transcription factor Ndt80 does not contribute to Mrr1-, Tac1-, and Upc2-mediated fluconazole resistance in Candida albicans. PLoS One 6: e25623.
78. Sato, T., Watanabe, T., Mikami, T., and Matsumoto, T. (2004) Farnesol, a morphogenetic autoregulatory substance in the dimorphic fungus Candida albicans, inhibits hyphae growth through suppression of a mitogen-activated protein kinase cascade. Biol Pharm Bull 27: 751–752.
79. Saville, S.P., Lazzell, A.L., Monteagudo, C., and Lopez-Ribot, J.L. (2003) Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot Cell 2: 1053–1060.
80. Savoldi, M., Malavazi, I., Soriani, F.M., Capellaro, J.L., Kitamoto, K., da Silva Ferreira, M.E., et al. (2008) Farnesol induces the transcriptional accumulation of the Aspergillus nidulans apoptosis-inducing factor (AIF)-like mitochondrial oxidoreductase. Mol Microbiol 70: 44–59.
81. Shapiro, R.S., Robbins, N., and Cowen, L.E. (2011) Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 75: 213–267.
82. Shareck, J., and Belhumeur, P. (2011) Modulation of morphogenesis in Candida albicans by various small molecules. Eukaryot Cell 10: 1004–1012.
83. Shchepin, R., Dumitru, R., Nickerson, K.W., Lund, M., and Dussault, P.H. (2005) Biologically active fluorescent farnesol analogs. Chem Biol 12: 639–641.
84. Shchepin, R., Hornby, J.M., Burger, E., Niessen, T., Dussault, P., and Nickerson, K.W. (2003) Quorum sensing in Candida albicans: probing farnesol's mode of action with 40 natural and synthetic farnesol analogs. Chem Biol 10: 743–750.
85. Shen, J., Cowen, L.E., Griffin, A.M., Chan, L., and Kohler, J.R. (2008) The Candida albicans pescadillo homolog is required for normal hypha-to-yeast morphogenesis and yeast proliferation. Proc Natl Acad Sci U S A 105: 20918–20923.
86. Shirtliff, M.E., Krom, B.P., Meijering, R.A., Peters, B.M., Zhu, J., Scheper, M.A., et al. (2009) Farnesol-induced apoptosis in Candida albicans. Antimicrob Agents Chemother 53: 2392–2401.
87. Smith, D.A., Nicholls, S., Morgan, B.A., Brown, A.J., and Quinn, J. (2004) A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans. Mol Biol Cell 15: 4179–4190.
88. Sudbery, P.E. (2011) Growth of Candida albicans hyphae. Nat Rev Microbiol 9: 737–748.
89. Sudbery, P., Gow, N., and Berman, J. (2004) The distinct morphogenic states of Candida albicans. Trends Microbiol 12: 317–324.
90. Tashiro, M., Kimura, S., Tateda, K., Saga, T., Ohno, A., Ishii, Y., et al. (2012) Pravastatin inhibits farnesol production in Candida albicans and improves survival in a mouse model of systemic candidiasis. Med Mycol 50: 353–360.
91. Uppuluri, P., Chaturvedi, A.K., Srinivasan, A., Banerjee, M., Ramasubramaniam, A.K., Kohler, J.R., et al. (2010) Dispersion as an important step in the Candida albicans biofilm developmental cycle. PLoS Pathog 6: e1000828.
92. Uppuluri, P., Mekala, S., and Chaffin, W.L. (2007) Farnesol-mediated inhibition of Candida albicans yeast growth and rescue by a diacylglycerol analogue. Yeast 24: 681–693.
93. Vinces, M.D., and Kumamoto, C.A. (2007) The morphogenetic regulator Czf1p is a DNA-binding protein that regulates white opaque switching in Candida albicans. Microbiology 153: 2877–2884.
94. Walther, A., and Wendland, J. (2003) An improved transformation protocol for the human fungal pathogen Candida albicans. Curr Genet 42: 339–343.
95. Weber, K., Schulz, B., and Ruhnke, M. (2010) The quorum-sensing molecule E,E-farnesol – its variable secretion and its impact on the growth and metabolism of Candida species. Yeast 27: 727–739.
96. Weber, K., Sohr, R., Schulz, B., Fleischhacker, M., and Ruhnke, M. (2008) Secretion of E,E-farnesol and biofilm formation in eight different Candida species. Antimicrob Agents Chemother 52: 1859–1861.
97. Wilson, D., and Hube, B. (2010) Hgc1 mediates dynamic Candida albicans-endothelium adhesion events during circulation. Eukaryot Cell 9: 278–287.
98. Wilson, D., Tutulan-Cunita, A., Jung, W., Hauser, N.C., Hernandez, R., Williamson, T., et al. (2007) Deletion of the high-affinity cAMP phosphodiesterase encoded by PDE2 affects stress responses and virulence in Candida albicans. Mol Microbiol 65: 841–856.
99. Yapar, N. (2014) Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag 10: 95–105.
100. Yu, L.H., Wei, X., Ma, M., Chen, X.J., and Xu, S.B. (2012) Possible inhibitory molecular mechanism of farnesol on the development of fluconazole resistance in Candida albicans biofilm. Antimicrob Agents Chemother 56: 770–775.
101. Zakikhany, K., Naglik, J.R., Schmidt-Westhausen, A., Holland, G., Schaller, M., and Hube, B. (2007) In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination. Cell Microbiol 9: 2938–2954.
102. Zeidler, U., Lettner, T., Lassnig, C., Muller, M., Lajko, R., Hintner, H., et al. (2008) UME6 is a crucial downstream target of other transcriptional regulators of true hyphal development in Candida albicans. FEMS Yeast Res 9: 126–142.
103. Zhang, L., Chang, W., Sun, B., Groh, M., Speicher, A., and Lou, H. (2011) Bisbibenzyls, a new type of antifungal agent, inhibit morphogenesis switch and biofilm formation through upregulation of DPP3 in Candida albicans. PLoS One 6: e28953.
104. Zheng, X., Wang, Y., and Wang, Y. (2004) Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis. EMBO J 23: 1845–1856.
105. Zhu, J., Krom, B.P., Sanglard, D., Intapa, C., Dawson, C.C., Peters, B.M., et al. (2011) Farnesol-induced apoptosis in Candida albicans is mediated by Cdr1-p extrusion and depletion of intracellular glutathione. PLoS One 6: e28830.
106. Zhu, W., and Filler, S.G. (2010) Interactions of Candida albicans with epithelial cells. Cell Microbiol 12: 273–282.
107. Zhu, Y., Fang, H.M., Wang, Y.M., Zeng, G.S., Zheng, X.D., and Wang, Y. (2009) Ras1 and Ras2 play antagonistic roles in regulating cellular cAMP level, stationary-phase entry and stress response in Candida albicans. Mol Microbiol 74: 862–875.