Ras signaling gets fine-tuned: Regulation of multiple pathogenic traits of Candida albicans

Eukaryotic Cell

Volumn 12, Issue 10, 2013, Pages 1316-1325

  Inglis, Diane O ^a   Sherlock, Gavin ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FUNGAL PROTEIN; RAS PROTEIN;

BIOFILM; CANDIDA ALBICANS; GENETICS; METABOLISM; PATHOGENICITY; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

BIOFILMS; CANDIDA ALBICANS; FUNGAL PROTEINS; RAS PROTEINS; SIGNAL TRANSDUCTION;

EID: 84884553759     PISSN: 15359778     EISSN: None     Source Type: Journal    
DOI: 10.1128/EC.00094-13     Document Type: Review

References (110)

1. Seneviratne CJ, Wang Y, Jin L, Wong SS, Herath TD, Samaranayake LP. 2012. Unraveling the resistance of microbial biofilms: has proteomics been helpful? Proteomics 12:651-665.
2. Vlamakis H, Chai Y, Beauregard P, Losick R, Kolter R. 2013. Sticking together: building a biofilm the Bacillus subtilis way. Nat. Rev. Microbiol. 11:157-168.
3. Verstraelen H, Swidsinski A. 2013. The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment. Curr. Opin. Infect. Dis. 26:86-89.
4. Islam MS, Richards JP, Ojha AK. 2012. Targeting drug tolerance in mycobacteria: a perspective from mycobacterial biofilms. Expert Rev. Anti Infect. Ther. 10:1055-1066.
5. Römling U, Balsalobre C. 2012. Biofilm infections, their resilience to therapy and innovative treatment strategies. J. Intern. Med. 272:541-561.
6. Walz JM, Memtsoudis SG, Heard SO. 2010. Prevention of central venous catheter bloodstream infections. J. Intensive Care Med. 25:131-138.
7. Cauda R. 2009. Candidaemia in patients with an inserted medical device. Drugs 69(Suppl 1):33-38.
8. Busscher HJ, Rinastiti M, Siswomihardjo W, van der Mei HC. 2010. Biofilm formation on dental restorative and implant materials. J. Dent. Res. 89:657-665.
9. Mah TF. 2012. Biofilm-specific antibiotic resistance. Future Microbiol. 7:1061-1072.
10. Ramage G, Rajendran R, Sherry L, Williams C. 2012. Fungal biofilm resistance. Int. J. Microbiol. 2012:528521. doi:10.1155/2012/528521.
11. Sardi JC, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJ. 2013. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J. Med. Microbiol. 62(Pt 1):10-24.
12. Douglas LJ. 2002. Medical importance of biofilms in Candida infections. Rev. Iberoam. Micol. 19:139-143.
13. Sudbery PE. 2011. Growth of Candida albicans hyphae. Nat. Rev. Microbiol. 9:737-748.
14. Biswas S, Van Dijck P, Datta A. 2007. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol. Mol. Biol. Rev. 71:348-376.
15. Whiteway M, Bachewich C. 2007. Morphogenesis in Candida albicans. Annu. Rev. Microbiol. 61:529-553.
16. Berman J. 2006. Morphogenesis and cell cycle progression in Candida albicans. Curr. Opin. Microbiol. 9:595-601.
17. Sudbery P, Gow N, Berman J. 2004. The distinct morphogenic states of Candida albicans. Trends Microbiol. 12:317-324.
18. Odds FC. 1985. Morphogenesis in Candida albicans. Crit. Rev. Microbiol. 12:45-93.
19. Lindsay AK, Deveau A, Piispanen AE, Hogan DA. 2012. Farnesol and cyclic AMP signaling effects on the hypha-to-yeast transition in Candida albicans. Eukaryot. Cell 11:1219-1225.
20. Hornby Jensen JM, Lisec AD, Tasto JJ, Jahnke B, Shoemaker R, Dussault P, Nickerson KW. 2001. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl. Environ. Microbiol. 67:2982-2992.
21. Han TL, Cannon RD, Villas-Bôas SG. 2012. The metabolic response of Candida albicans to farnesol under hyphae-inducing conditions. FEMS Yeast Res. 12:879-889.
22. Lo HJ, Köhler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR. 1997. Nonfilamentous C. albicans mutants are avirulent. Cell 90: 939-949.
23. Saville SP, Lazzell AL, Monteagudo C, Lopez-Ribot JL. 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.
24. Carlisle PL, Banerjee M, Lazzell A, Monteagudo C, López-Ribot JL, Kadosh D. 2009. Expression levels of a filament-specific transcriptional regulator are sufficient to determine Candida albicans morphology and virulence. Proc. Natl. Acad. Sci. U. S. A. 106:599-604.
25. Nobile CJ, Andes DR, Nett JE, Smith FJ, Yue F, Phan QT, Edwards JE, Filler SG, Mitchell AP. 2006. Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog. 2:e63. doi:10.1371/journal.ppat.0020063.
26. Hoyer LL, Payne TL, Bell M, Myers AM, Scherer S. 1998. Candida albicans ALS3 and insights into the nature of the ALS gene family. Curr. Genet. 33:451-459.
27. Miller MG, Johnson AD. 2002. White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110:293-302.
28. Levitt MD, Bond JH, Jr. 1970. Volume, composition, and source of intestinal gas. Gastroenterology 59:921-929.
29. 2 and dependent upon the Ras1-cyclic AMP pathway. Eukaryot. Cell 11:1257-1267.
30. Baines AT, Xu D, Der CJ. 2011. Inhibition of Ras for cancer treatment: the search continues. Future Med. Chem. 3:1787-1808.
31. Poulogiannis G, Luo F, Arends MJ. 2012. RAS signalling in the colorectum in health and disease. Cell Commun. Adhes. 19:1-9.
32. Cullen PJ, Sprague GF, Jr. 2012. The regulation of filamentous growth in yeast. Genetics 190:23-49.
33. Broach JR. 2012. Nutritional control of growth and development in yeast. Genetics 192:73-105.
34. de la Torre-Ruiz Mozo-Villarías A, Pujol N, Petkova MI. 2010. How budding yeast sense and transduce the oxidative stress signal and the impact in cell growth and morphogenesis. Curr. Protein Pept. Sci. 11: 669-679.
35. Alspaugh JA, Cavallo LM, Perfect JR, Heitman J. 2000. RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Mol. Microbiol. 36:352-365.
36. Piispanen AE, Bonnefoi O, Carden S, Deveau A, Bassilana M, Hogan DA. 2011. Roles of Ras1 membrane localization during Candida albicans hyphal growth and farnesol response. Eukaryot. Cell 10:1473-1484.
37. Prior Hancock IA, JF. 2012. Ras trafficking, localization and compartmentalized signalling. Semin. Cell Dev. Biol. 23:145-153.
38. Fang HM, Wang Y. 2006. RA domain-mediated interaction of Cdc35 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development. Mol. Microbiol. 61:484-496.
39. 2 sensing with cAMP signaling and virulence. Curr. Biol. 15:2021-2026.
40. Bockmühl DP, Ernst JF. 2001. A potential phosphorylation site for an A-type kinase in the Efg1 regulator protein contributes to hyphal morphogenesis of Candida albicans. Genetics 157:1523-1530.
41. Bahn Y, Staab J, 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.
42. Bahn YS, Molenda M, Staab JF, Lyman CA, Gordon LJ, Sundstrom P. 2007. Genome-wide transcriptional profiling of the cyclic AMPdependent signaling pathway during morphogenic transitions of Candida albicans. Eukaryot. Cell 6:2376-2390.
43. Bahn YS, 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.
44. Jung WH, Warn P, Ragni E, Popolo L, Nunn CD, Turner MP, 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.
45. Wilson D, Fiori A, Brucker KD, Van Dijck P, Stateva L. 2010. Candida albicans Pde1p and Gpa2p comprise a regulatory module mediating agonist-induced cAMP signalling and environmental adaptation. Fungal Genet. Biol. 47:742-752.
46. Leberer E, Harcus D, Dignard D, Johnson L, Ushinsky S, Thomas DY, Schröppel K. 2001. Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans. Mol. Microbiol. 42:673-687.
47. Piispanen AE, Grahl N, Hollomon JM, Hogan DA. 2013. Regulated proteolysis of Candida albicans Ras1 is involved in morphogenesis and quorum sensing regulation. Mol. Microbiol. 89:166-178.
48. Zhu Y, Fang HM, Wang YM, Zeng GS, Zheng XD, 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.
49. Park H, Myers CL, Sheppard DC, Phan QT, Sanchez AA, Edwards J, Filler SG. 2005. Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell. Microbiol. 7:499-510.
50. Rocha CR, Schröppel K, Harcus D, Marcil A, Dignard D, Taylor BN, Thomas DY, Whiteway M, Leberer E. 2001. Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans. Mol. Biol. Cell 12:3631-3643.
51. Hogan DA, Mühlschlegel FA. 2011. Candida albicans developmental regulation: adenylyl cyclase as a coincidence detector of parallel signals. Curr. Opin. Microbiol. 14:682-686.
52. Hogan DA, Sundstrom P. 2009. The Ras/cAMP/PKA signaling pathway and virulence in Candida albicans. Future Microbiol. 4:1263-1270.
53. Finkel JS, Xu W, Huang D, Hill EM, Desai JV, Woolford CA, Nett JE, Taff H, Norice CT, Andes DR, Lanni F, Mitchell AP. 2012. Portrait of Candida albicans adherence regulators. PLoS Pathog. 8:e1002525. doi:10.1371/journal.ppat.1002525.
54. Nobile CJ, Fox EP, Nett JE, Sorrells TR, Mitrovich QM, Hernday AD, Tuch BB, Andes DR, Johnson AD. 2012. A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148:126-138.
55. Carlisle PL, Kadosh D. 2013. A genome-wide transcriptional analysis of morphology determination in Candida albicans. Mol. Biol. Cell 24:246-260.
56. Lohse MB, Hernday AD, Fordyce PM, Noiman L, Sorrells TR, Hanson-Smith V, Nobile CJ, Derisi JL, Johnson AD. 2013. Identification and characterization of a previously undescribed family of sequencespecific DNA-binding domains. Proc. Natl. Acad. Sci. U. S. A. 110:7660-7665.
57. Tuch BB, Mitrovich QM, Homann OR, Hernday AD, Monighetti CK, De La Vega FM, Johnson AD. 2010. The transcriptomes of two heritable cell types illuminate the circuit governing their differentiation. PLoS Genet. 6:e1001070. doi:10.1371/journal.pgen.1001070.
58. Lohse MB, Johnson AD. 2010. Temporal anatomy of an epigenetic switch in cell programming: the white-opaque transition of C. albicans. Mol. Microbiol. 78:331-343.
59. Doedt T, Krishnamurthy S, Bockmühl DP, Tebarth B, Stempel C, Russell CL, Brown AJ, Ernst JF. 2004. APSES proteins regulate morphogenesis and metabolism in Candida albicans. Mol. Biol. Cell 15:3167-3180.
60. Nobile CJ, Mitchell AP. 2005. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p. Curr. Biol. 15:1150-1155.
61. Li F, Palecek SP. 2005. Identification of Candida albicans genes that induce Saccharomyces cerevisiae cell adhesion and morphogenesis. Biotechnol. Prog. 21:1601-1609.
62. Heilmann CJ, Sorgo AG, Siliakus AR, Dekker HL, Brul S, de Koster CG, de Koning LJ, Klis FM. 2011. Hyphal induction in the human fungal pathogen Candida albicans reveals a characteristic wall protein profile. Microbiology 157(Pt 8):2297-2307.
63. Sheppard DC, Yeaman MR, Welch WH, Phan QT, Fu Y, Ibrahim AS, Filler SG, Zhang M, Waring AJ, Edwards JE, Jr. 2004. Functional and structural diversity in the Als protein family of Candida albicans. J. Biol. Chem. 279:30480-30489.
64. Nobbs AH, Vickerman MM, Jenkinson HF. 2010. Heterologous expression of Candida albicans cell wall-associated adhesins in Saccharomyces cerevisiae reveals differential specificities in adherence and biofilm formation and in binding oral Streptococcus gordonii. Eukaryot. Cell 9:1622-1634.
65. Fanning S, Xu W, Solis N, Woolford CA, Filler SG, Mitchell AP. 2012. Divergent targets of Candida albicans biofilm regulator Bcr1 in vitro and in vivo. Eukaryot. Cell 11:896-904.
66. Martin R, Albrecht-Eckardt D, Brunke S, Hube B, Hünniger K, Kurzai O. 2013. A core filamentation response network in Candida albicans is restricted to eight genes. PLoS One 8:e58613. doi:10.1371/journal.pone.0058613.
67. Kadosh D, Johnson AD. 2005. Induction of the Candida albicans filamentous growth program by relief of transcriptional repression: a genome-wide analysis. Mol. Biol. Cell 16:2903-2912.
68. Cleary IA, Reinhard SM, Miller CL, Murdoch C, Thornhill MH, Lazzell AL, Monteagudo C, Thomas DP, Saville SP. 2011. Candida albicans adhesin Als3p is dispensable for virulence in the mouse model of disseminated candidiasis. Microbiology 157(Pt 6):1806-1815.
69. Sharkey LL, McNemar MD, Saporito-Irwin SM, Sypherd PS, Fonzi WA. 1999. HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1. J. Bacteriol. 181: 5273-5279.
70. Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA. 2001. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J. Bacteriol. 183:5385-5394.
71. Mukherjee PK, Zhou G, Munyon R, Ghannoum MA. 2005. Candida biofilm: a well-designed protected environment. Med. Mycol. 43:191-208.
72. Chandra J, Mukherjee PK, Leidich SD, Faddoul FF, Hoyer LL, Douglas LJ, Ghannoum MA. 2001. Antifungal resistance of candidal biofilms formed on denture acrylic in vitro. J. Dent. Res. 80:903-908.
73. Fox EP, Nobile CJ. 2012. A sticky situation: untangling the transcriptional network controlling biofilm development in Candida albicans. Transcription 3:315-322.
74. Soll DR. 2008. Candida biofilms: is adhesion sexy? Curr. Biol. 18:R717-R720.
75. Yi S, Sahni N, Daniels KJ, Lu KL, Srikantha T, Huang G, Garnaas AM, Soll DR. 2011. Alternative mating type configurations (a/α versus a/a or α/α) of Candida albicans result in alternative biofilms regulated by different pathways. PLoS Biol. 9:e1001117. doi:10.1371/journal.pbio.1001117.
76. Sellam A, Askew C, Epp E, Tebbji F, Mullick A, Whiteway M, Nantel A. 2010. Role of transcription factor CaNdt80p in cell separation, hyphal growth, and virulence in Candida albicans. Eukaryot. Cell 9:634-644.
77. Lu Y, Su C, Liu H. 2012. A GATA transcription factor recruits Hda1 in response to reduced Tor1 signaling to establish a hyphal chromatin state in Candida albicans. PLoS Pathog. 8:e1002663. doi:10.1371/journal.ppat.1002663.
78. Brown AJ, Gow NA. 1999. Regulatory networks controlling Candida albicans morphogenesis. Trends Microbiol. 7:333-338.
79. Odds FC. 1988. Candida and candidosis, 2nd ed. Bailliere Tindall, London, United Kingdom.
80. Taschdjian CL, Burchall JJ, Kozinn PJ. 1960. Rapid identification of Candida albicans by filamentation on serum and serum substitutes. AMA J. Dis. Child. 99:212-215.
81. Berman J, Sudbery PE. 2002. Candida albicans: a molecular revolution built on lessons from budding yeast. Nat. Rev. Genet. 3:918-930.
82. Buffo J, Herman MA, Soll DR. 1984. A characterization of pHregulated dimorphism in Candida albicans. Mycopathologia 85:21-30.
83. Hrmová M, Drobnica L. 1982. Induction of mycelial type of development in Candida albicans by the antibiotic monorden and N-acetyl-Dglucosamine. Mycopathologia 79:55-64.
84. Mattia E, Carruba G, Angiolella L, Cassone A. 1982. Induction of germ tube formation by N-acetyl-D-glucosamine in Candida albicans: uptake of inducer and germinative response. J. Bacteriol. 152:555-562.
85. Simonetti N, Strippoli V, Cassone A. 1974. Yeast-mycelial conversion induced by N-acetyl-D-glucosamine in Candida albicans. Nature 250: 344-346.
86. Mock RC, Pollack JH, Hashimoto T. 1990. Carbon dioxide induces endotrophic germ tube formation in Candida albicans. Can. J. Microbiol. 36:249-253.
87. Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR, Heitman J, Cowen LE. 2009. Hsp90 orchestrates temperaturedependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr. Biol. 19:621-629.
88. Banerjee M, Thompson DS, Lazzell A, Carlisle PL, Pierce C, Monteagudo C, López-Ribot JL, Kadosh D. 2008. UME6, a novel filamentspecific regulator of Candida albicans hyphal extension and virulence. Mol. Biol. Cell 19:1354-1365.
89. Zeidler U, Lettner T, Lassnig C, Müller M, Lajko R, Hintner H, Breitenbach M, Bito A. 2009. UME6 is a crucial downstream target of other transcriptional regulators of true hyphal development in Candida albicans. FEMS Yeast Res. 9:126-142.
90. Lu Y, Su C, Wang A, Liu H. 2011. Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance. PLoS Biol. 9:e1001105. doi:10.1371 /journal.pbio.1001105.
91. Lassak T, Schneider E, Bussmann M, Kurtz D, Manak JR, Srikantha T, Soll DR, Ernst JF. 2011. Target specificity of the Candida albicans Efg1 regulator. Mol. Microbiol. 82:602-618.
92. Harcus D, Nantel A, Marcil A, Rigby T, Whiteway M. 2004. Transcription profiling of cyclic AMP signaling in Candida albicans. Mol. Biol. Cell 15:4490-4499.
93. Inglis DO, Johnson AD. 2002. Ash1 protein, an asymmetrically localized transcriptional regulator, controls filamentous growth and virulence of Candida albicans. Mol. Cell. Biol. 22:8669-8680.
94. Kelly MT, MacCallum DM, Clancy SD, Odds FC, Brown AJ, Butler G. 2004. The Candida albicans CaACE2 gene affects morphogenesis, adherence and virulence. Mol. Microbiol. 53:969-983.
95. Hnisz D, Bardet AF, Nobile CJ, Petryshyn A, Glaser W, Schöck U, Stark A, Kuchler K. 2012. A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis. PLoS Genet. 8:e1003118. doi:10.1371/journal.pgen.1003118.
96. Srikantha T, Tsai L, Daniels K, Klar AJ, Soll DR. 2001. The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans. J. Bacteriol. 183:4614-4625.
97. Hnisz D, Majer O, Frohner IE, Komnenovic V, Kuchler K. 2010. The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans. PLoS Pathog. 6:e1000889. doi:10.1371/journal.ppat.1000889.
98. Slutsky B, Buffo J, Soll DR. 1985. High-frequency switching of colony morphology in Candida albicans. Science 230:666-669.
99. Anderson J, Soll DR. 1987. Unique phenotype of opaque cells in the white-opaque transition of Candida albicans. J. Bacteriol. 169:5579-5588.
100. Kolotila MP, Diamond RD. 1990. Effects of neutrophils and in vitro oxidants on survival and phenotypic switching of Candida albicans WO-1. Infect. Immun. 58:1174-1179.
101. Lan CY, Newport G, Murillo LA, Jones T, Scherer S, Davis RW, Agabian N. 2002. Metabolic specialization associated with phenotypic switching in Candida albicans. Proc. Natl. Acad. Sci. U. S. A. 99:14907-14912.
102. Geiger J, Wessels D, Lockhart SR, Soll DR. 2004. Release of a potent polymorphonuclear leukocyte chemoattractant is regulated by whiteopaque switching in Candida albicans. Infect. Immun. 72:667-677.
103. Lohse MB, Johnson AD. 2008. Differential phagocytosis of white versus opaque Candida albicans by Drosophila and mouse phagocytes. PLoS One 3:e1473. doi:10.1371/journal.pone.0001473.
104. 2 and 37°C stabilize the less virulent opaque cell of Candida albicans. Chin. Med. J. (Engl) 123:2446-2450.
105. Lockhart SR, Pujol C, Daniels KJ, Miller MG, Johnson AD, Pfaller MA, Soll DR. 2002. In Candida albicans, white-opaque switchers are homozygous for mating type. Genetics 162:737-745.
106. Huang G, Yi S, Sahni N, Daniels KJ, Srikantha T, Soll DR. 2010. N-Acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans. PLoS Pathog. 6:e1000806.
107. Huang G, Srikantha T, Sahni N, Yi S, Soll DR. 2009. CO(2) regulates white-to-opaque switching in Candida albicans. Curr. Biol. 19:330-334.
108. Bockmühl DP, Krishnamurthy S, Gerads M, Sonneborn A, Ernst JF. 2001. Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans. Mol. Microbiol. 42:1243-1257.
109. Cloutier M, Castilla R, Bolduc N, Zelada A, Martineau P, Bouillon M, Magee BB, Passeron S, Giasson L, Cantore ML. 2003. The two isoforms of the cAMP-dependent protein kinase catalytic subunit are involved in the control of dimorphism in the human fungal pathogen Candida albicans. Fungal Genet. Biol. 38:133-141.
110. Zordan RE, Miller MG, Galgoczy DJ, Tuch BB, Johnson AD. 2007. Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans. PLoS Biol. 5:e256. doi:10.1371/journal.pbio.0050256.