title: Regulation of white-opaque switching in Candida albicans.
abstract: The yeast Candida albicans is part of the microflora in most healthy people, but can become a pathogen when host defenses are compromised. The phenotypic plasticity of C. albicans, which includes switching between different morphologies, contributes to its ability to colonize and infect virtually all body locations. A particularly fascinating developmental program is white-opaque switching, a reversible transition between the normal yeast morphology (white) and an elongated cell type (opaque), which is the mating-competent form of this fungus. Although opaque cells are much less able than white cells to cause a systemic infection, they are better adapted for colonization of specific host niches, like skin. White-opaque switching is controlled by the mating type locus (MTL), which in most C. albicans strains exists in two alleles, MTLa and MTL. These strains produce a heterodimeric repressor, a1-alpha2, which suppresses switching to the opaque phase by inhibiting expression of the master regulator Wor1. Loss of MTL heterozygosity relieves this repression, a mechanism that ensures that only MTL homozygous cells can switch to the mating-competent opaque form. Several transcriptional feedback loops, including positive autoregulation of Wor1, result in bistable expression of the master regulator (low in white and high in opaque cells) and epigenetic inheritance of the two phases. White-opaque switching occurs stochastically at a low frequency, but certain environmental conditions can drive the switch from one phase to the other by affecting either the activity of the transcriptional feedback loops or accumulation of Wor1 protein in a cell. Such environmental regulation of phenotypic switching may restrict mating to suitable host niches, while allowing a C. albicans population to withstand the various challenges encountered in different tissues.
authors.affiliation: Institut für Molekulare Infektionsbiologie, Universität Würzburg, Josef-Schneider-Str. 2, Würzburg, Germany. joachim.morschhaeuser@mail.uni-wuerzburg.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Morschhäuser
mesh_terms: D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D049770:Genes, Mating Type, Fungal; D006801:Humans; D010641:Phenotype; D014158:Transcription, Genetic; D014774:Virulence
references.citation: Curr Opin Microbiol. 2009 Aug;12(4):371-6
references.pmid: 19535285
references.citation: Nat Rev Microbiol. 2003 Nov;1(2):106-16
references.pmid: 15035040
references.citation: Mol Cell Biol. 1992 Jul;12(7):2997-3005
references.pmid: 1620110
references.citation: Mol Microbiol. 2009 Oct;74(1):1-15
references.pmid: 19555456
references.citation: Mol Microbiol. 2004 Jun;52(5):1451-62
references.pmid: 15165246
references.citation: PLoS One. 2008 Jan 23;3(1):e1473
references.pmid: 18213381
references.citation: Cell. 2002 Aug 9;110(3):293-302
references.pmid: 12176317
references.citation: Science. 2000 Jul 14;289(5477):307-10
references.pmid: 10894780
references.citation: Cell Microbiol. 2005 Nov;7(11):1546-54
references.pmid: 16207242
references.citation: Mol Microbiol. 1999 Nov;34(4):651-62
references.pmid: 10564506
references.citation: Eukaryot Cell. 2004 Jun;3(3):764-75
references.pmid: 15189997
references.citation: Infect Immun. 1993 May;61(5):1823-8
references.pmid: 8478072
references.citation: Infect Immun. 1990 May;58(5):1174-9
references.pmid: 2157666
references.citation: Eukaryot Cell. 2006 Oct;5(10):1674-87
references.pmid: 16950924
references.citation: EMBO J. 2006 May 17;25(10):2240-52
references.pmid: 16628217
references.citation: J Bacteriol. 2000 Mar;182(6):1580-91
references.pmid: 10692363
references.citation: PLoS Biol. 2007 Oct;5(10):e256
references.pmid: 17880264
references.citation: Genetics. 2005 Mar;169(3):1311-27
references.pmid: 15654090
references.citation: Curr Biol. 2009 Feb 24;19(4):330-4
references.pmid: 19200725
references.citation: Genetics. 2002 Oct;162(2):737-45
references.pmid: 12399384
references.citation: FEMS Yeast Res. 2009 Oct;9(7):973-89
references.pmid: 19744246
references.citation: J Bacteriol. 1987 Jan;169(1):189-97
references.pmid: 3539914
references.citation: Mol Biol Cell. 2009 Jul;20(14):3178-91
references.pmid: 19458191
references.citation: Curr Opin Microbiol. 2009 Dec;12(6):650-4
references.pmid: 19853498
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12813-8
references.pmid: 16905649
references.citation: Infect Immun. 1997 Nov;65(11):4468-75
references.pmid: 9353021
references.citation: Infect Immun. 1999 Dec;67(12):6652-62
references.pmid: 10569787
references.citation: Bioessays. 2004 Jan;26(1):10-20
references.pmid: 14696036
references.citation: Infect Immun. 2004 Feb;72(2):667-77
references.pmid: 14742507
references.citation: Genetics. 2001 Jun;158(2):919-24
references.pmid: 11404352
references.citation: Cell. 2003 Nov 14;115(4):389-99
references.pmid: 14622594
references.citation: J Bacteriol. 2001 Jun;183(12):3761-9
references.pmid: 11371541
references.citation: Mol Microbiol. 2007 Jun;64(6):1587-604
references.pmid: 17555440
references.citation: PLoS Pathog. 2008 Jun 13;4(6):e1000089
references.pmid: 18551173
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14907-12
references.pmid: 12397174
references.citation: Curr Biol. 2005 Nov 22;15(22):2021-6
references.pmid: 16303561
references.citation: Eukaryot Cell. 2007 Mar;6(3):465-72
references.pmid: 17259544
references.citation: J Bacteriol. 2001 Aug;183(15):4614-25
references.pmid: 11443097
references.citation: Mycopathologia. 1988 Jun;102(3):149-56
references.pmid: 3050525
references.citation: EMBO J. 2003 May 15;22(10):2505-15
references.pmid: 12743044
references.citation: Cell Microbiol. 2002 Aug;4(8):461-9
references.pmid: 12174081
references.citation: Mol Microbiol. 2005 Dec;58(5):1288-302
references.pmid: 16313617
references.citation: Genetics. 2006 Sep;174(1):191-201
references.pmid: 16783004
references.citation: J Gen Microbiol. 1990 Oct;136(10):1925-36
references.pmid: 2269869
references.citation: Mol Genet Genomics. 2004 Aug;272(1):88-97
references.pmid: 15249973
references.citation: Clin Microbiol Rev. 1992 Apr;5(2):183-203
references.pmid: 1576587
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12807-12
references.pmid: 16899543
references.citation: Microbiology (Reading). 2007 Sep;153(Pt 9):2877-2884
references.pmid: 17768232
references.citation: Infect Immun. 1989 Feb;57(2):458-67
references.pmid: 2643570
references.citation: J Gen Microbiol. 1989 May;135(5):1201-8
references.pmid: 2695598
references.citation: Infect Immun. 1999 Sep;67(9):4655-60
references.pmid: 10456912
references.citation: J Bacteriol. 1988 Feb;170(2):895-9
references.pmid: 2828333
references.citation: Infect Immun. 2003 Sep;71(9):4970-6
references.pmid: 12933839
references.citation: Gene. 1993 Sep 6;131(1):53-60
references.pmid: 7916716
references.citation: PLoS Biol. 2008 Feb;6(2):e38
references.pmid: 18303948