title: Genetic control of conventional and pheromone-stimulated biofilm formation in Candida albicans.
abstract: Candida albicans can stochastically switch between two phenotypes, white and opaque. Opaque cells are the sexually competent form of C. albicans and therefore undergo efficient polarized growth and mating in the presence of pheromone. In contrast, white cells cannot mate, but are induced - under a specialized set of conditions - to form biofilms in response to pheromone. In this work, we compare the genetic regulation of such "pheromone-stimulated" biofilms with that of "conventional" C. albicans biofilms. In particular, we examined a network of six transcriptional regulators (Bcr1, Brg1, Efg1, Tec1, Ndt80, and Rob1) that mediate conventional biofilm formation for their potential roles in pheromone-stimulated biofilm formation. We show that four of the six transcription factors (Bcr1, Brg1, Rob1, and Tec1) promote formation of both conventional and pheromone-stimulated biofilms, indicating they play general roles in cell cohesion and biofilm development. In addition, we identify the master transcriptional regulator of pheromone-stimulated biofilms as C. albicans Cph1, ortholog of Saccharomyces cerevisiae Ste12. Cph1 regulates mating in C. albicans opaque cells, and here we show that Cph1 is also essential for pheromone-stimulated biofilm formation in white cells. In contrast, Cph1 is dispensable for the formation of conventional biofilms. The regulation of pheromone- stimulated biofilm formation was further investigated by transcriptional profiling and genetic analyses. These studies identified 196 genes that are induced by pheromone signaling during biofilm formation. One of these genes, HGC1, is shown to be required for both conventional and pheromone-stimulated biofilm formation. Taken together, these observations compare and contrast the regulation of conventional and pheromone-stimulated biofilm formation in C. albicans, and demonstrate that Cph1 is required for the latter, but not the former.
authors: Department of Microbiology and Immunology, Brown University, Providence, Rhode Island, United States of America.
authors: Ching-Hsuan
authors: CH
authors: Lin
authors: Shail
authors: S
authors: Kabrawala
authors: Emily P
authors: EP
authors: Fox
authors: Clarissa J
authors: CJ
authors: Nobile
authors: Alexander D
authors: AD
authors: Johnson
authors: Richard J
authors: RJ
authors: Bennett
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D010641:Phenotype; D010675:Pheromones / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: C090837:CPH1 protein, Candida albicans; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; C495215:Ndt80 protein, Candida albicans; D010675:Pheromones; C489432:TEC1 protein, Candida albicans; D014157:Transcription Factors
references: Microbiol Mol Biol Rev. 2000 Dec;64(4):746-85
references: 11104818
references: Cell. 2003 Nov 14;115(4):389-99
references: 14622594
references: Mol Biol Cell. 2008 Mar;19(3):957-70
references: 18162580
references: EMBO J. 2004 Apr 21;23(8):1845-56
references: 15071502
references: Cell. 2002 Aug 9;110(3):293-302
references: 12176317
references: Genes Dev. 1993 Aug;7(8):1584-97
references: 8339934
references: BMC Genomics. 2011 Apr 15;12:192
references: 21496229
references: PLoS Pathog. 2010 Mar 12;6(3):e1000806
references: 20300604
references: Curr Biol. 2009 Jun 9;19(11):891-9
references: 19446455
references: PLoS Genet. 2010 Aug 19;6(8):e1001070
references: 20808890
references: Cell. 2004 Dec 29;119(7):981-90
references: 15620356
references: Eukaryot Cell. 2003 Dec;2(6):1350-60
references: 14665468
references: Eukaryot Cell. 2006 Oct;5(10):1674-87
references: 16950924
references: EMBO J. 2006 May 17;25(10):2240-52
references: 16628217
references: PLoS Pathog. 2012 Feb;8(2):e1002525
references: 22359502
references: Nature. 2010 Dec 16;468(7326):959-63
references: 21164485
references: Nat Rev Microbiol. 2011 Feb;9(2):109-18
references: 21189476
references: Curr Biol. 2009 Feb 24;19(4):330-4
references: 19200725
references: Genetics. 2002 Oct;162(2):737-45
references: 12399384
references: Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21158-63
references: 22158989
references: Cell. 2003 May 2;113(3):395-404
references: 12732146
references: J Bacteriol. 1987 Jan;169(1):189-97
references: 3539914
references: Genes Dev. 1989 Sep;3(9):1349-61
references: 2558054
references: Mol Microbiol. 2006 Oct;62(1):100-19
references: 16987174
references: Curr Opin Microbiol. 2009 Dec;12(6):650-4
references: 19853498
references: Trends Microbiol. 2011 Jan;19(1):8-13
references: 21036616
references: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12813-8
references: 16905649
references: J Bacteriol. 1990 Jan;172(1):224-35
references: 2403540
references: Mol Biol Cell. 2009 Jul;20(14):3178-91
references: 19458191
references: Cell. 2012 Jan 20;148(1-2):126-38
references: 22265407
references: PLoS Pathog. 2009 Oct;5(10):e1000601
references: 19798425
references: Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2510-5
references: 21262815
references: Genetics. 2000 May;155(1):17-29
references: 10790381
references: Antimicrob Agents Chemother. 2004 Dec;48(12):4505-12
references: 15561818
references: J Bacteriol. 1987 Dec;169(12):5579-88
references: 3316187
references: Eukaryot Cell. 2003 Oct;2(5):847-55
references: 14555467
references: Science. 1994 Dec 9;266(5191):1723-6
references: 7992058
references: Cell Microbiol. 2006 Sep;8(9):1382-91
references: 16848788
references: Nature. 2009 Aug 13;460(7257):890-3
references: 19675652
references: Infect Immun. 1979 Oct;26(1):348-54
references: 387610
references: Mol Microbiol. 2002 Dec;46(5):1335-44
references: 12453219
references: PLoS Biol. 2010 May 04;8(5):e1000363
references: 20454615
references: Mol Biol Cell. 2009 Jul;20(14):3363-73
references: 19477921
references: Curr Biol. 2005 Jun 21;15(12):1150-5
references: 15964282
references: Eukaryot Cell. 2005 Feb;4(2):298-309
references: 15701792
references: Dev Cell. 2007 Sep;13(3):421-32
references: 17765684
references: Mol Cell Biol. 2003 Nov;23(22):8189-201
references: 14585977
references: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12807-12
references: 16899543
references: Eukaryot Cell. 2010 Apr;9(4):634-44
references: 20097739
references: Eukaryot Cell. 2004 Aug;3(4):1015-27
references: 15302834
references: Eukaryot Cell. 2005 Sep;4(9):1562-73
references: 16151249
references: Eukaryot Cell. 2009 Dec;8(12):1909-13
references: 19837954
references: Mol Biol Cell. 2011 Dec;22(24):4918-30
references: 21998194
references: Mol Microbiol. 2002 Dec;46(5):1345-51
references: 12453220
references: Gene. 2004 Oct 27;341:119-27
references: 15474295
references: J Bacteriol. 1988 Feb;170(2):895-9
references: 2828333
references: Curr Biol. 2007 May 15;17(10):R349-53
references: 17502083