Genetics, Vol. 156, 31-44, September 2000, Copyright © 2000

Identification and Characterization of TUP1-Regulated Genes in Candida albicans

Burkhard R. Brauna, W. Steven Headb, Ming X. Wangb, and Alexander D. Johnsona
a Department of Microbiology, University of California, San Francisco, California 94143-0414
b Vanderbilt Medical School, Department of Ophthalmology and Visual Science, Nashville, Tennessee 37323-8808

Corresponding author: Burkhard R. Braun, Department of Microbiology, S-410, University of California, 513 Parnassus Ave., San Francisco, CA 94143-0414., braun{at}socrates.ucsf.edu (E-mail)

Communicating editor: A. P. MITCHELL

TUP1 encodes a transcriptional repressor that negatively controls filamentous growth in Candida albicans. Using subtractive hybridization, we identified six genes, termed repressed by TUP1 (RBT), whose expression is regulated by TUP1. One of the genes (HWP1) has previously been characterized, and a seventh TUP1-repressed gene (WAP1) was recovered due to its high similarity to RBT5. These genes all encode secreted or cell surface proteins, and four out of the seven (HWP1, RBT1, RBT5, and WAP1) encode putatively GPI-modified cell wall proteins. The remaining three, RBT2, RBT4, and RBT7, encode, respectively, an apparent ferric reductase, a plant pathogenesis-related protein (PR-1), and a putative secreted RNase T2. The expression of RBT1, RBT4, RBT5, HWP1, and WAP1 was induced in wild-type cells during the switch from the yeast form to filamentous growth, indicating the importance of TUP1 in regulating this process and implicating the RBTs in hyphal-specific functions. We produced knockout strains in C. albicans for RBT1, RBT2, RBT4, RBT5, and WAP1 and detected no phenotypes on several laboratory media. However, two animal models for C. albicans infection, a rabbit cornea model and a mouse systemic infection model, revealed that rbt1{Delta} and rbt4{Delta} strains had significantly reduced virulence. TUP1 appears, therefore, to regulate many genes in C. albicans, a significant fraction of which are induced during filamentous growth, and some of which participate in pathogenesis.




This article has been cited by other articles:


Home page
 Eukaryot CellHome page
Y.-U. Baek, M. Li, and D. A. Davis
Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors
Eukaryot. Cell, July 1, 2008; 7(7): 1168 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
S. Goyard, P. Knechtle, M. Chauvel, A. Mallet, M.-C. Prevost, C. Proux, J.-Y. Coppee, P. Schwartz, F. Dromer, H. Park, et al.
The Yak1 Kinase Is Involved in the Initiation and Maintenance of Hyphal Growth in Candida albicans
Mol. Biol. Cell, May 1, 2008; 19(5): 2251 - 2266.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
M. Banerjee, D. S. Thompson, A. Lazzell, P. L. Carlisle, C. Pierce, C. Monteagudo, J. L. Lopez-Ribot, and D. Kadosh
UME6, a Novel Filament-specific Regulator of Candida albicans Hyphal Extension and Virulence
Mol. Biol. Cell, April 1, 2008; 19(4): 1354 - 1365.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
G. J. Sosinska, P. W. J. de Groot, M. J. Teixeira de Mattos, H. L. Dekker, C. G. de Koster, K. J. Hellingwerf, and F. M. Klis
Hypoxic conditions and iron restriction affect the cell-wall proteome of Candida albicans grown under vagina-simulative conditions
Microbiology, February 1, 2008; 154(2): 510 - 520.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
Y.-S. Bahn, M. Molenda, J. F. Staab, C. A. Lyman, L. J. Gordon, and P. Sundstrom
Genome-Wide Transcriptional Profiling of the Cyclic AMP-Dependent Signaling Pathway during Morphogenic Transitions of Candida albicans
Eukaryot. Cell, December 1, 2007; 6(12): 2376 - 2390.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
Y. Li, C. Su, X. Mao, F. Cao, and J. Chen
Roles of Candida albicans Sfl1 in Hyphal Development
Eukaryot. Cell, November 1, 2007; 6(11): 2112 - 2121.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
J. Bauer and J. Wendland
Candida albicans Sfl1 Suppresses Flocculation and Filamentation
Eukaryot. Cell, October 1, 2007; 6(10): 1736 - 1744.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
C. Westwater, E. Balish, T. F. Warner, P. J. Nicholas, E. E. Paulling, and D. A. Schofield
Susceptibility of gnotobiotic transgenic mice (Tg{epsilon}26) with combined deficiencies in natural killer cells and T cells to wild-type and hyphal signalling-defective mutants of Candida albicans
J. Med. Microbiol., September 1, 2007; 56(9): 1138 - 1144.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. R. Borneman, T. A. Gianoulis, Z. D. Zhang, H. Yu, J. Rozowsky, M. R. Seringhaus, L. Y. Wang, M. Gerstein, and M. Snyder
Divergence of Transcription Factor Binding Sites Across Related Yeast Species
Science, August 10, 2007; 317(5839): 815 - 819.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
C. Ding and G. Butler
Development of a Gene Knockout System in Candida parapsilosis Reveals a Conserved Role for BCR1 in Biofilm Formation
Eukaryot. Cell, August 1, 2007; 6(8): 1310 - 1319.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
S. Biswas, P. Van Dijck, and A. Datta
Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans
Microbiol. Mol. Biol. Rev., June 1, 2007; 71(2): 348 - 376.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
B. E. Jackson, B. M. Mitchell, and K. R. Wilhelmus
Corneal Virulence of Candida albicans Strains Deficient in Tup1-Regulated Genes
Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2535 - 2539.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
S. Argimon, J. A. Wishart, R. Leng, S. Macaskill, A. Mavor, T. Alexandris, S. Nicholls, A. W. Knight, B. Enjalbert, R. Walmsley, et al.
Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans
Eukaryot. Cell, April 1, 2007; 6(4): 682 - 692.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
M. L. Richard and A. Plaine
Comprehensive Analysis of Glycosylphosphatidylinositol-Anchored Proteins in Candida albicans
Eukaryot. Cell, February 1, 2007; 6(2): 119 - 133.
[Full Text] [PDF]

Home page
 MicrobiologyHome page
S. A. B. Knight and A. Dancis
Reduction of 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) is dependent on CaFRE10 ferric reductase for Candida albicans grown in unbuffered media.
Microbiology, August 1, 2006; 152(Pt 8): 2301 - 2308.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
K. W. Nickerson, A. L. Atkin, and J. M. Hornby
Quorum sensing in dimorphic fungi: farnesol and beyond.
Appl. Envir. Microbiol., June 1, 2006; 72(6): 3805 - 3813.
[Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. Clemente-Blanco, A. Gonzalez-Novo, F. Machin, D. Caballero-Lima, L. Aragon, M. Sanchez, C. R. V. de Aldana, J. Jimenez, and J. Correa-Bordes
The Cdc14p phosphatase affects late cell-cycle events and morphogenesis in Candida albicans
J. Cell Sci., March 15, 2006; 119(6): 1130 - 1143.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
B. Eisman, R. Alonso-Monge, E. Roman, D. Arana, C. Nombela, and J. Pla
The Cek1 and Hog1 Mitogen-Activated Protein Kinases Play Complementary Roles in Cell Wall Biogenesis and Chlamydospore Formation in the Fungal Pathogen Candida albicans
Eukaryot. Cell, February 1, 2006; 5(2): 347 - 358.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
B. S. Hromatka, S. M. Noble, and A. D. Johnson
Transcriptional Response of Candida albicans to Nitric Oxide and the Role of the YHB1 Gene in Nitrosative Stress and Virulence
Mol. Biol. Cell, October 1, 2005; 16(10): 4814 - 4826.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. A. B. Knight, G. Vilaire, E. Lesuisse, and A. Dancis
Iron Acquisition from Transferrin by Candida albicans Depends on the Reductive Pathway
Infect. Immun., September 1, 2005; 73(9): 5482 - 5492.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
R. Zhao, K. J. Daniels, S. R. Lockhart, K. M. Yeater, L. L. Hoyer, and D. R. Soll
Unique Aspects of Gene Expression during Candida albicans Mating and Possible G1 Dependency
Eukaryot. Cell, July 1, 2005; 4(7): 1175 - 1190.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
D. Kadosh and A. D. Johnson
Induction of the Candida albicans Filamentous Growth Program by Relief of Transcriptional Repression: A Genome-wide Analysis
Mol. Biol. Cell, June 1, 2005; 16(6): 2903 - 2912.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
S. Garcia-Sanchez, A. L. Mavor, C. L. Russell, S. Argimon, P. Dennison, B. Enjalbert, and A. J.P. Brown
Global Roles of Ssn6 in Tup1- and Nrg1-dependent Gene Regulation in the Fungal Pathogen, Candida albicans
Mol. Biol. Cell, June 1, 2005; 16(6): 2913 - 2925.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
M. Bassilana, J. Hopkins, and R. A. Arkowitz
Regulation of the Cdc42/Cdc24 GTPase Module during Candida albicans Hyphal Growth
Eukaryot. Cell, March 1, 2005; 4(3): 588 - 603.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
Y.-Y. Cao, Y.-B. Cao, Z. Xu, K. Ying, Y. Li, Y. Xie, Z.-Y. Zhu, W.-S. Chen, and Y.-Y. Jiang
cDNA Microarray Analysis of Differential Gene Expression in Candida albicans Biofilm Exposed to Farnesol
Antimicrob. Agents Chemother., February 1, 2005; 49(2): 584 - 589.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
G. Moran, C. Stokes, S. Thewes, B. Hube, D. C. Coleman, and D. Sullivan
Comparative genomics using Candida albicans DNA microarrays reveals absence and divergence of virulence-associated genes in Candida dubliniensis
Microbiology, October 1, 2004; 150(10): 3363 - 3382.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. F. Staab, Y.-S. Bahn, C.-H. Tai, P. F. Cook, and P. Sundstrom
Expression of Transglutaminase Substrate Activity on Candida albicans Germ Tubes through a Coiled, Disulfide-bonded N-terminal Domain of Hwp1 Requires C-terminal Glycosylphosphatidylinositol Modification
J. Biol. Chem., September 24, 2004; 279(39): 40737 - 40747.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
A. Brand, D. M. MacCallum, A. J. P. Brown, N. A. R. Gow, and F. C. Odds
Ectopic Expression of URA3 Can Influence the Virulence Phenotypes and Proteome of Candida albicans but Can Be Overcome by Targeted Reintegration of URA3 at the RPS10 Locus
Eukaryot. Cell, August 1, 2004; 3(4): 900 - 909.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
T. Miwa, Y. Takagi, M. Shinozaki, C.-W. Yun, W. A. Schell, J. R. Perfect, H. Kumagai, and H. Tamaki
Gpr1, a Putative G-Protein-Coupled Receptor, Regulates Morphogenesis and Hypha Formation in the Pathogenic Fungus Candida albicans
Eukaryot. Cell, August 1, 2004; 3(4): 919 - 931.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
P. W. J. de Groot, A. D. de Boer, J. Cunningham, H. L. Dekker, L. de Jong, K. J. Hellingwerf, C. de Koster, and F. M. Klis
Proteomic Analysis of Candida albicans Cell Walls Reveals Covalently Bound Carbohydrate-Active Enzymes and Adhesins
Eukaryot. Cell, August 1, 2004; 3(4): 955 - 965.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
T. Doedt, S. Krishnamurthy, D. P. Bockmuhl, B. Tebarth, C. Stempel, C. L. Russell, A. J.P. Brown, and J. F. Ernst
APSES Proteins Regulate Morphogenesis and Metabolism in Candida albicans
Mol. Biol. Cell, July 1, 2004; 15(7): 3167 - 3180.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
H. Lotz, K. Sohn, H. Brunner, F. A. Muhlschlegel, and S. Rupp
RBR1, a Novel pH-Regulated Cell Wall Gene of Candida albicans, Is Repressed by RIM101 and Activated by NRG1
Eukaryot. Cell, June 1, 2004; 3(3): 776 - 784.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
H. Johannesson, P. Vidal, J. Guarro, R. A. Herr, G. T. Cole, and J. W. Taylor
Positive Directional Selection in the Proline-Rich Antigen (PRA) Gene Among the Human Pathogenic Fungi Coccidioides immitis, C. posadasii and Their Closest Relatives
Mol. Biol. Evol., June 1, 2004; 21(6): 1134 - 1145.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
P. Staib, A. Binder, M. Kretschmar, T. Nichterlein, K. Schroppel, and J. Morschhauser
Tec1p-Independent Activation of a Hypha-Associated Candida albicans Virulence Gene during Infection
Infect. Immun., April 1, 2004; 72(4): 2386 - 2389.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
A. Cassola, M. Parrot, S. Silberstein, B. B. Magee, S. Passeron, L. Giasson, and M. L. Cantore
Candida albicans Lacking the Gene Encoding the Regulatory Subunit of Protein Kinase A Displays a Defect in Hyphal Formation and an Altered Localization of the Catalytic Subunit
Eukaryot. Cell, February 1, 2004; 3(1): 190 - 199.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. A. Sanchez, D. A. Johnston, C. Myers, J. E. Edwards Jr., A. P. Mitchell, and S. G. Filler
Relationship between Candida albicans Virulence during Experimental Hematogenously Disseminated Infection and Endothelial Cell Damage In Vitro
Infect. Immun., January 1, 2004; 72(1): 598 - 601.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. J. Bennett, M. A. Uhl, M. G. Miller, and A. D. Johnson
Identification and Characterization of a Candida albicans Mating Pheromone
Mol. Cell. Biol., November 15, 2003; 23(22): 8189 - 8201.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
S. P. Saville, A. L. Lazzell, C. Monteagudo, and J. L. Lopez-Ribot
Engineered Control of Cell Morphology In Vivo Reveals Distinct Roles for Yeast and Filamentous Forms of Candida albicans during Infection
Eukaryot. Cell, October 1, 2003; 2(5): 1053 - 1060.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
M. Niewerth, D. Kunze, M. Seibold, M. Schaller, H. C. Korting, and B. Hube
Ciclopirox Olamine Treatment Affects the Expression Pattern of Candida albicans Genes Encoding Virulence Factors, Iron Metabolism Proteins, and Drug Resistance Factors
Antimicrob. Agents Chemother., June 1, 2003; 47(6): 1805 - 1817.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
E. S. Bensen, S. G. Filler, and J. Berman
A Forkhead Transcription Factor Is Important for True Hyphal as well as Yeast Morphogenesis in Candida albicans
Eukaryot. Cell, October 1, 2002; 1(5): 787 - 798.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
A. Nantel, D. Dignard, C. Bachewich, D. Harcus, A. Marcil, A.-P. Bouin, C. W. Sensen, H. Hogues, M. van het Hoog, P. Gordon, et al.
Transcription Profiling of Candida albicans Cells Undergoing the Yeast-to-Hyphal Transition
Mol. Biol. Cell, October 1, 2002; 13(10): 3452 - 3465.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
B. R. Steen, T. Lian, S. Zuyderduyn, W. K. MacDonald, M. Marra, S. J.M. Jones, and J. W. Kronstad
Temperature-Regulated Transcription in the Pathogenic Fungus Cryptococcus neoformans
Genome Res., September 1, 2002; 12(9): 1386 - 1400.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C.-J. Hu, C. Bai, X.-D. Zheng, Y.-M. Wang, and Y. Wang
Characterization and Functional Analysis of the Siderophore-Iron Transporter CaArn1p in Candida albicans
J. Biol. Chem., August 16, 2002; 277(34): 30598 - 30605.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
T. Peng, L. Shubitz, J. Simons, R. Perrill, K. I. Orsborn, and J. N. Galgiani
Localization within a Proline-Rich Antigen (Ag2/PRA) of Protective Antigenicity against Infection with Coccidioides immitis in Mice
Infect. Immun., July 1, 2002; 70(7): 3330 - 3335.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
R. Zhao, S. R. Lockhart, K. Daniels, and D. R. Soll
Roles of TUP1 in Switching, Phase Maintenance, and Phase-Specific Gene Expression in Candida albicans
Eukaryot. Cell, June 1, 2002; 1(3): 353 - 365.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. D. Giusani, M. Vinces, and C. A. Kumamoto
Invasive Filamentous Growth of Candida albicans Is Promoted by Czf1p-Dependent Relief of Efg1p-Mediated Repression
Genetics, April 1, 2002; 160(4): 1749 - 1753.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
P. Staib, M. Kretschmar, T. Nichterlein, H. Hof, and J. Morschhauser
Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the Candida albicans Virulence Gene SAP5 during Infection
Infect. Immun., February 1, 2002; 70(2): 921 - 927.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
S. A. B. Knight, E. Lesuisse, R. Stearman, R. D. Klausner, and A. Dancis
Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator
Microbiology, January 1, 2002; 148(1): 29 - 40.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Lane, S. Zhou, T. Pan, Q. Dai, and H. Liu
The Basic Helix-Loop-Helix Transcription Factor Cph2 Regulates Hyphal Development in Candida albicans Partly via Tec1
Mol. Cell. Biol., October 1, 2001; 21(19): 6418 - 6428.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
P. Leng, P. R. Lee, H. Wu, and A. J. P. Brown
Efg1, a Morphogenetic Regulator in Candida albicans, Is a Sequence-Specific DNA Binding Protein
J. Bacteriol., July 1, 2001; 183(13): 4090 - 4093.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
D. Kadosh and A. D. Johnson
Rfg1, a Protein Related to the Saccharomyces cerevisiae Hypoxic Regulator Rox1, Controls Filamentous Growth and Virulence in Candida albicans
Mol. Cell. Biol., April 1, 2001; 21(7): 2496 - 2505.
[Abstract] [Full Text]

Home page
 GeneticsHome page
R. A. Khalaf and R. S. Zitomer
The DNA Binding Protein Rfg1 Is a Repressor of Filamentation in Candida albicans
Genetics, April 1, 2001; 157(4): 1503 - 1512.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
S. Lane, C. Birse, S. Zhou, R. Matson, and H. Liu
DNA Array Studies Demonstrate Convergent Regulation of Virulence Factors by Cph1, Cph2, and Efg1 in Candida albicans
J. Biol. Chem., December 21, 2001; 276(52): 48988 - 48996.
[Abstract] [Full Text] [PDF]