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Morphogenesis in C. albicans

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Candida albicans: Cellular and Molecular Biology

Abstract

Many human fungal pathogens possess the ability to grow in a variety of different morphologies and Candida albicans is no exception. In dimorphic fungal pathogens, such as Histoplasma capsulatum and Coccidioides immitis, morphological transitions are critical for virulence (Klein and Tebbets, Curr Opin Microbiol, 10(4):314–319, 2007). However, other pathogens, such as Candida glabrata, rarely alter their morphology and the ability to change shape appears to play little, if any, role in their pathogenicity (Do Carmo-Sousa 1969; Fidel et al., Clin Microbiol Rev 12:80–96, 1999; Csank and Haynes, FEMS Microbiol Lett 189(1):115–120, 2000). The ability of Candida albicans to undergo a reversible morphological transition from yeast to filamentous form represents a fundamental aspect of this pathogen’s biology. This transition is typically correlated with pathogenicity and important for a wide variety of virulence-related processes (Lo et al., Cell 90(5):939–949, 1997; Braun and Johnson, Science 277(5322):105–109, 1997; Braun et al., Genetics 156(1):31–44, 2000; Saville et al., Eukaryot Cell 2(5):1053–1060, 2003; Carlisle et al., Proc Natl Acad Sci USA 106:599–604, 2009; Kumamoto and Vinces, Proc Natl Acad Sci USA 102(15):5576–5581, 2005; Korting et al., J Med Microbiol 52(Pt 8):623–632, 2003; Gow et al., Curr opin microbiol 5(4):366–371, 2002). As a consequence, a significant amount of research, mostly over the past 25 years, has focused on signaling pathways, regulators, and mechanisms that are involved in controlling the C. albicans morphological transition. In this chapter we will first describe the major C. albicans morphologies and the relationship between C. albicans morphology and virulence. Next, we will discuss the mechanics of hyphal growth as well as a variety of signaling pathways, regulators, and mechanisms important for regulating C. albicans morphogenesis in response to host environmental cues. Finally, we will discuss recent insights gained from genome-wide studies of the C. albicans morphological transition as well as the potential that this transition may hold to serve as a target for new therapeutic strategies.

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References

  • Alonso-Monge R, Navarro-Garcia F, Molero G, Diez-Orejas R, Gustin M, Pla J, Sanchez M, Nombela C (1999) Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans. J Bacteriol 181(10):3058–3068

    CAS  PubMed  PubMed Central  Google Scholar 

  • Alvarez FJ, Konopka JB (2007) Identification of an N-acetylglucosamine transporter that mediates hyphal induction in Candida albicans. Mol Biol Cell 18(3):965–975. doi:E06-10-0931 [pii]10.1091/mbc.E06-10-0931

  • Argimon S, Wishart JA, Leng R, Macaskill S, Mavor A, Alexandris T, Nicholls S, Knight AW, Enjalbert B, Walmsley R, Odds FC, Gow NA, Brown AJ (2007) Developmental regulation of an adhesin gene during cellular morphogenesis in the fungal pathogen Candida albicans. Eukaryot Cell 6(4):682–692. doi:EC.00340-06 [pii]10.1128/EC.00340-06

  • Bachewich C, Whiteway M (2005) Cyclin Cln3p links G1 progression to hyphal and pseudohyphal development in Candida albicans. Eukaryot Cell 4(1):95–102. doi:4/1/95 [pii]10.1128/EC.4.1.95-102.2005

  • Bachewich C, Thomas DY, Whiteway M (2003) Depletion of a polo-like kinase in Candida albicans activates cyclase-dependent hyphal-like growth. Mol Biol Cell 14(5):2163–2180. doi:10.1091/mbc.02-05-0076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banerjee M, Thompson DS, Lazzell A, Carlisle PL, Pierce C, Monteagudo C, Lopez-Ribot JL, Kadosh D (2008) UME6, a novel filament-specific regulator of Candida albicans hyphal extension and virulence. Mol Biol Cell 19(4):1354–1365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barelle CJ, Bohula EA, Kron SJ, Wessels D, Soll DR, Schafer A, Brown AJ, Gow NA (2003) Asynchronous cell cycle and asymmetric vacuolar inheritance in true hyphae of Candida albicans. Eukaryot Cell 2(3):398–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bartnicki-Garcia S, Bartnicki DD, Gierz G, Lopez-Franco R, Bracker CE (1995) Evidence that Spitzenkorper behavior determines the shape of a fungal hypha: a test of the hyphoid model. Exp Mycol 19(2):153–159

    Article  CAS  PubMed  Google Scholar 

  • Barwell KJ, Boysen JH, Xu W, Mitchell AP (2005) Relationship of DFG16 to the Rim101p pH response pathway in Saccharomyces cerevisiae and Candida albicans. Eukaryot Cell 4(5):890–899. doi:10.1128/EC.4.5.890-899.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bassilana M, Arkowitz RA (2006) Rac1 and Cdc42 have different roles in Candida albicans development. Eukaryot Cell 5(2):321–329. doi:10.1128/EC.5.2.321-329.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bassilana M, Blyth J, Arkowitz RA (2003) Cdc24, the GDP-GTP exchange factor for Cdc42, is required for invasive hyphal growth of Candida albicans. Eukaryot Cell 2(1):9–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bassilana M, Hopkins J, Arkowitz RA (2005) Regulation of the Cdc42/Cdc24 GTPase module during Candida albicans hyphal growth. Eukaryot Cell 4(3):588–603. doi:10.1128/EC.4.3.588-603.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bensen ES, Filler SG, Berman J (2002) A forkhead transcription factor is important for true hyphal as well as yeast morphogenesis in Candida albicans. Eukaryot Cell 1(5):787–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bensen ES, Clemente-Blanco A, Finley KR, Correa-Bordes J, Berman J (2005) The mitotic cyclins Clb2p and Clb4p affect morphogenesis in Candida albicans. Mol Biol Cell 16(7):3387–3400. doi:E04-12-1081 [pii]10.1091/mbc.E04-12-1081

  • Bharucha N, Chabrier-Rosello Y, Xu T, Johnson C, Sobczynski S, Song Q, Dobry CJ, Eckwahl MJ, Anderson CP, Benjamin AJ, Kumar A, Krysan DJ (2011) A large-scale complex haploinsufficiency-based genetic interaction screen in Candida albicans: analysis of the RAM network during morphogenesis. PLoS Genet 7(4):e1002058. doi:10.1371/journal.pgen.1002058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bishop A, Lane R, Beniston R, Chapa-y-Lazo B, Smythe C, Sudbery P (2010) Hyphal growth in Candida albicans requires the phosphorylation of Sec2 by the Cdc28-Ccn1/Hgc1 kinase. EMBO J 29(17):2930–2942. doi:10.1038/emboj.2010.158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biswas K, Morschhauser J (2005) The Mep2p ammonium permease controls nitrogen starvation-induced filamentous growth in Candida albicans. Mol Microbiol 56(3):649–669. doi:MMI4576 [pii]10.1111/j.1365-2958.2005.04576.x

  • Bockmuhl 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(4):1523–1530

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bockmuhl 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(5):1243–1257. doi:2688 [pii]

    Google Scholar 

  • Bramley TA, Menzies GS, Williams RJ, Kinsman OS, Adams DJ (1991) Binding sites for LH in Candida albicans: comparison with the mammalian corpus luteum LH receptor. J Endocrinol 130(2):177–190

    Article  CAS  PubMed  Google Scholar 

  • Braun BR, Johnson AD (1997) Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 277(5322):105–109

    Article  CAS  PubMed  Google Scholar 

  • Braun BR, Head WS, Wang MX, Johnson AD (2000) Identification and characterization of TUP1-regulated genes in Candida albicans. Genetics 156(1):31–44

    CAS  PubMed  PubMed Central  Google Scholar 

  • Braun BR, Kadosh D, Johnson AD (2001) NRG1, a repressor of filamentous growth in C. albicans, is down-regulated during filament induction. EMBO J 20:4753–4761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown AJ (2002) Expression of growth form-specific factors during morphogenesis in Candida albicans. In: Calderone RA (ed) Candida and Candidiasis. ASM Press, Washington, D.C., pp 87–93

    Google Scholar 

  • Brown DH Jr, Giusani AD, Chen X, Kumamoto CA (1999) Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene. Mol Microbiol 34(4):651–662

    Article  CAS  PubMed  Google Scholar 

  • Bruno VM, Wang Z, Marjani SL, Euskirchen GM, Martin J, Sherlock G, Snyder M (2010) Comprehensive annotation of the transcriptome of the human fungal pathogen Candida albicans using RNA-seq. Genome Res 20(10):1451–1458. doi:gr.109553.110 [pii]10.1101/gr.109553.110

  • Carlisle PL, 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(9):1320–1328. doi:EC.00046-10 [pii]10.1128/EC.00046-10

  • Carlisle PL, Kadosh D (2013) A genome-wide transcriptional analysis of morphology determination in Candida albicans. Mol Biol Cell 24(3):246–260. doi:10.1091/mbc.E12-01-0065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carlisle PL, Banerjee M, Lazzell A, Monteagudo C, Lopez-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 USA 106:599–604

    Article  CAS  PubMed  Google Scholar 

  • Caticha O, Grover S, Winge D, Odell WD (1992) Stimulation of Candida albicans transition by human chorionic gonadotrophin and a bacterial protein. Endocr Res 18(2):133–143

    Article  CAS  PubMed  Google Scholar 

  • Chabasse D, Bouchara JP, de Gentile L, Chennebault JM (1988) Candida albicans chlamydospores observed in vivo in a patient with AIDS. Ann Biol Clin (Paris) 46(10):817–818

    CAS  Google Scholar 

  • 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(18):5385–5394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chapa y Lazo B, Bates S, Sudbery P (2005) The G1 cyclin Cln3 regulates morphogenesis in Candida albicans. Eukaryot Cell 4(1):90–94. doi:10.1128/EC.4.1.90-94.2005

  • Childers DS, Mundodi V, Banerjee M, Kadosh D (2014) A 5’ UTR-mediated translational efficiency mechanism inhibits the Candida albicans morphological transition. Mol Microbiol 92(3):570–585. doi:10.1111/mmi.12576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chou H, Glory A, Bachewich C (2011) Orthologues of the anaphase-promoting complex/cyclosome coactivators Cdc20p and Cdh1p are important for mitotic progression and morphogenesis in Candida albicans. Eukaryot Cell 10(5):696–709. doi:10.1128/EC.00263-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cleary IA, Lazzell AL, Monteagudo C, Thomas DP, Saville SP (2012) BRG1 and NRG1 form a novel feedback circuit regulating Candida albicans hypha formation and virulence. Mol Microbiol 85(3):557–573. doi:10.1111/j.1365-2958.2012.08127.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cole GT, Seshan KR, Phaneuf M, Lynn KT (1991) Chlamydospore-like cells of Candida albicans in the gastrointestinal tract of infected, immunocompromised mice. Can J Microbiol 37(8):637–646

    Article  CAS  PubMed  Google Scholar 

  • Court H, Sudbery P (2007) Regulation of Cdc42 GTPase activity in the formation of hyphae in Candida albicans. Mol Biol Cell 18(1):265–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crampin H, Finley K, Gerami-Nejad M, Court H, Gale C, Berman J, Sudbery P (2005) Candida albicans hyphae have a Spitzenkorper that is distinct from the polarisome found in yeast and pseudohyphae. J Cell Sci 118(Pt 13):2935–2947

    Article  CAS  PubMed  Google Scholar 

  • Csank C, Haynes K (2000) Candida glabrata displays pseudohyphal growth. FEMS Microbiol Lett 189(1):115–120. doi:S0378-1097(00)00241-X [pii]

    Google Scholar 

  • Davis D (2003) Adaptation to environmental pH in Candida albicans and its relation to pathogenesis. Curr Genet 44(1):1–7. doi:10.1007/s00294-003-0415-2

    Article  CAS  PubMed  Google Scholar 

  • Davis D, Edwards JE Jr, Mitchell AP, Ibrahim AS (2000a) Candida albicans RIM101 pH response pathway is required for host-pathogen interactions. Infect Immun 68(10):5953–5959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis D, Wilson RB, Mitchell AP (2000b) RIM101-dependent and -independent pathways govern pH responses in Candida albicans. Mol Cell Biol 20:971–978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiDomenico BJ, Brown NH, Lupisella J, Greene JR, Yanko M, Koltin Y (1994) Homologs of the yeast neck filament associated genes.In: Isolation and sequence analysis of Candida albicans CDC3 and CDC10. Mol Gen Genet 242(6):689–698

    Article  CAS  PubMed  Google Scholar 

  • Do Carmo-Sousa L (1969) Distribution of yeasts in nature. In: Rose AH, Harrison JS (eds) The Yeasts, vol 1. Academic Press, pp 79–105

    Google Scholar 

  • Dunkler A, Wendland J (2007) Candida albicans Rho-type GTPase-encoding genes required for polarized cell growth and cell separation. Eukaryot Cell 6(5):844–854. doi:10.1128/EC.00201-06

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Enjalbert B, Smith DA, Cornell MJ, Alam I, Nicholls S, Brown AJ, Quinn J (2006) Role of the Hog1 stress-activated protein kinase in the global transcriptional response to stress in the fungal pathogen Candida albicans. Mol Biol Cell 17(2):1018–1032. doi:10.1091/mbc.E05-06-0501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fazly A, Jain C, Dehner AC, Issi L, Lilly EA, Ali A, Cao H, Fidel PL Jr, Rao RP, Kaufman PD (2013) Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis. Proc Natl Acad Sci USA 110(33):13594–13599. doi:10.1073/pnas.1305982110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fidel PLJ, al. e (1999) Candida glabrata: a review of epidemiology, pathogenesis, and clinical disease. Clin Microbiol Rev 12:80–96

    Google Scholar 

  • Frohner IE, Bourgeois C, Yatsyk K, Majer O, Kuchler K (2009) Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance. Mol Microbiol 71(1):240–252. doi:MMI6528 [pii]10.1111/j.1365-2958.2008.06528.x

  • Gale CA, Berman J (2012) Cell cycle and growth control in Candida species. In: Calderone RA, Clancy CJ (eds) Candida and Candidiasis. ASM Press, Washington, D.C., pp 101–124

    Chapter  Google Scholar 

  • Gantner BN, Simmons RM, Underhill DM (2005) Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 24(6):1277–1286

    Google Scholar 

  • Geiger J, Wessels D, Lockhart SR, Soll DR (2004) Release of a potent polymorphonuclear leukocyte chemoattractant is regulated by white-opaque switching in Candida albicans. Infect Immun 72(2):667–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Novo A, Correa-Bordes J, Labrador L, Sanchez M, Vazquez de Aldana CR, Jimenez J (2008) Sep7 is essential to modify septin ring dynamics and inhibit cell separation during Candida albicans hyphal growth. Mol Biol Cell 19(4):1509–1518. doi:E07-09-0876 [pii]10.1091/mbc.E07-09-0876

  • Gow NA (1997) Germ tube growth of Candida albicans. Curr Top Med Mycol 8(1–2):43–55

    CAS  PubMed  Google Scholar 

  • Gow NA, Gooday GW (1984) A model for the germ tube formation and mycelial growth form of Candida albicans. Sabouraudia 22(2):137–144

    Article  CAS  PubMed  Google Scholar 

  • Gow NA, Henderson G, Gooday GW (1986) Cytological interrelationships between the cell cycle and duplication cycle of Candida albicans. Microbios 47(191):97–105

    CAS  PubMed  Google Scholar 

  • Gow NA, Perera TH, Sherwood-Higham J, Gooday GW, Gregory DW, Marshall D (1994) Investigation of touch-sensitive responses by hyphae of the human pathogenic fungus Candida albicans. Scan Microsc 8(3):705–710

    CAS  Google Scholar 

  • Gow NA, Brown AJ, Odds FC (2002) Fungal morphogenesis and host invasion. Curr opin microbiol 5(4):366–371. doi:S1369527402003387 [pii]

    Google Scholar 

  • Hall RA, De Sordi L, Maccallum DM, Topal H, Eaton R, Bloor JW, Robinson GK, Levin LR, Buck J, Wang Y, Gow NA, Steegborn C, Muhlschlegel FA (2010) CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans. PLoS Pathog 6(11):e1001193. doi:10.1371/journal.ppat.1001193

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hall RA, Turner KJ, Chaloupka J, Cottier F, De Sordi L, Sanglard D, Levin LR, Buck J, Muhlschlegel FA (2011) The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans. Eukaryot Cell 10(8):1034–1042. doi:10.1128/EC.05060-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hope H, Bogliolo S, Arkowitz RA, Bassilana M (2008) Activation of Rac1 by the guanine nucleotide exchange factor Dck1 is required for invasive filamentous growth in the pathogen Candida albicans. Mol Biol Cell 19(9):3638–3651. doi:10.1091/mbc.E07-12-1272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hope H, Schmauch C, Arkowitz RA, Bassilana M (2010) The Candida albicans ELMO homologue functions together with Rac1 and Dck1, upstream of the MAP Kinase Cek1, in invasive filamentous growth. Mol Microbiol 76(6):1572–1590. doi:10.1111/j.1365-2958.2010.07186.x

    Article  CAS  PubMed  Google Scholar 

  • 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(6):451–459

    Article  CAS  PubMed  Google Scholar 

  • Huang G, Srikantha T, Sahni N, Yi S, Soll DR (2009) CO(2) regulates white-to-opaque switching in Candida albicans. Curr Biol 19(4):330–334. doi:10.1016/j.cub.2009.01.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(3):e1000806. doi:10.1371/journal.ppat.1000806

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hube B (1996) Candida albicans secreted aspartyl proteinases. Curr Top Med Mycol 7(1):55–69

    CAS  PubMed  Google Scholar 

  • Hube B, Naglik J (2002) Extracellular hydrolases. In: Calderone RA (ed) Candida and Candidiasis. ASM Press, Washington, D.C., pp 107–122

    Google Scholar 

  • Johnson A (2003) The biology of mating in Candida albicans. Nat Rev Microbiol 1(2):106–116. doi:10.1038/nrmicro752

    Article  CAS  PubMed  Google Scholar 

  • Jones LA, Sudbery PE (2010) Spitzenkorper, exocyst, and polarisome components in Candida albicans hyphae show different patterns of localization and have distinct dynamic properties. Eukaryot Cell 9(10):1455–1465. doi:10.1128/EC.00109-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jong AY, Stins MF, Huang SH, Chen SH, Kim KS (2001) Traversal of Candida albicans across human blood-brain barrier in vitro. Infect Immun 69(7):4536–4544. doi:10.1128/IAI.69.7.4536-4544.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kadosh D, Johnson AD (2001) Rfg1, a protein related to the Saccharomyces cerevisiae hypoxic regulator Rox1, controls filamentous growth and virulence in Candida albicans. Mol Cell Biol 21:2496–2505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(6):2903–2912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(3):969–983. doi:10.1111/j.1365-2958.2004.04185.xMMI4185 [pii]

  • Khalaf RA, Zitomer RS (2001) The DNA binding protein Rfg1 is a repressor of filamentation in Candida albicans. Genet 157(4):1503–1512

    CAS  Google Scholar 

  • Kinsman OS, Pitblado K, Coulson CJ (1988) Effect of mammalian steroid hormones and luteinizing hormone on the germination of Candida albicans and implications for vaginal candidosis. Mycoses 31(12):617–626

    Article  CAS  PubMed  Google Scholar 

  • Klein BS, Tebbets B (2007) Dimorphism and virulence in fungi. Curr Opin Microbiol 10(4):314–319. doi:S1369-5274(07)00080-X [pii]10.1016/j.mib.2007.04.002

  • Korting HC, Hube B, Oberbauer S, Januschke E, Hamm G, Albrecht A, Borelli C, Schaller M (2003) Reduced expression of the hyphal-independent Candida albicans proteinase genes SAP1 and SAP3 in the efg1 mutant is associated with attenuated virulence during infection of oral epithelium. J Med Microbiol 52(Pt 8):623–632

    Article  CAS  PubMed  Google Scholar 

  • Kullas AL, Li M, Davis DA (2004) Snf7p, a component of the ESCRT-III protein complex, is an upstream member of the RIM101 pathway in Candida albicans. Eukaryot Cell 3(6):1609–1618. doi:10.1128/EC.3.6.1609-1618.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumamoto CA (2005) A contact-activated kinase signals Candida albicans invasive growth and biofilm development. Proc Natl Acad Sci USA 102(15):5576–5581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumamoto CA, Vinces MD (2005) Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence. Cell Microbiol 7(11):1546–1554

    Article  CAS  PubMed  Google Scholar 

  • 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 USA 99(23):14907–14912. doi:10.1073/pnas.232566499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leberer E, Harcus D, Broadbent ID, Clark KL, Dignard D, Ziegelbauer K, Schmidt A, Gow NAR, Brown AJP, Thomas DY (1996) Signal transduction through homologues of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. Proc Natl Acad Sci USA 93:13217–13222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leberer E, Harcus D, Dignard D, Johnson L, Ushinsky S, Thomas DY, Schroppel 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(3):673–687

    Article  CAS  PubMed  Google Scholar 

  • Leng P, Lee PR, Wu H, Brown AJ (2001) Efg1, a morphogenetic regulator in Candida albicans, is a sequence-specific DNA binding protein. J Bacteriol 183(13):4090–4093. doi:10.1128/JB.183.13.4090-4093.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, Martin SJ, Bruno VM, Mitchell AP, Davis DA (2004) Candida albicans Rim13p, a protease required for Rim101p processing at acidic and alkaline pHs. Eukaryot Cell 3(3):741–751. doi:10.1128/EC.3.3.741-751.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Kohler J, Fink GR (1994) Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Sci 266(5191):1723–1726

    Article  CAS  Google Scholar 

  • Lo HJ, Kohler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR (1997) Nonfilamentous C. albicans mutants are avirulent. Cell 90(5):939–949

    Article  CAS  PubMed  Google Scholar 

  • Lohse MB, Johnson AD (2008) Differential phagocytosis of white versus opaque Candida albicans by Drosophila and mouse phagocytes. PLoS ONE 3(1):e1473. doi:10.1371/journal.pone.0001473

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lohse MB, Johnson AD (2009) White-opaque switching in Candida albicans. Curr Opin Microbiol 12(6):650–654. doi:S1369-5274(09)00144-1 [pii]10.1016/j.mib.2009.09.010

  • 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 sequence-specific DNA-binding domains. Proc Natl Acad Sci USA 110(19):7660–7665. doi:10.1073/pnas.1221734110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Franco R, Bartnicki-Garcia S, Bracker CE (1994) Pulsed growth of fungal hyphal tips. Proc Natl Acad Sci USA 91(25):12228–12232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(7):e1001105. doi:10.1371/journal.pbio.1001105 PBIOLOGY-D-10–01188 [pii]

  • 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(4):e1002663. doi:10.1371/journal.ppat.1002663 PPATHOGENS-D-11–02628 [pii]

  • Lu Y, Su C, Solis NV, Filler SG, Liu H (2013) Synergistic regulation of hyphal elongation by hypoxia, CO2, and nutrient conditions controls the virulence of Candida albicans. Cell Host Microbe 14(5):499–509. doi:10.1016/j.chom.2013.10.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y, Su C, Unoje O, Liu H (2014) Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation. Proc Natl Acad Sci USA 111(5):1975–1980. doi:10.1073/pnas.1318690111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maidan MM, Thevelein JM, Van Dijck P (2005) Carbon source induced yeast-to-hypha transition in Candida albicans is dependent on the presence of amino acids and on the G-protein-coupled receptor Gpr1. Biochem Soc Trans 33(Pt 1):291–293. doi:10.1042/BST0330291

    Article  CAS  PubMed  Google Scholar 

  • Martchenko M, Alarco AM, Harcus D, Whiteway M (2004) Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene. Mol Biol Cell 15(2):456–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin R, Walther A, Wendland J (2005) Ras1-induced hyphal development in Candida albicans requires the formin Bni1. Eukaryot Cell 4(10):1712–1724. doi:10.1128/EC.4.10.1712-1724.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merson-Davies LA, Odds FC (1989) A morphology index for characterization of cell shape in Candida albicans. J Gen Microbiol 135(Pt 11)):3143–3152

    Google Scholar 

  • 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(3):293–302. doi:S0092867402008371 [pii]

    Google Scholar 

  • Mitchell BM, Wu TG, Jackson BE, Wilhelmus KR (2007) Candida albicans strain-dependent virulence and Rim13p-mediated filamentation in experimental keratomycosis. Invest Ophthalmol Vis Sci 48(2):774–780. doi:10.1167/iovs.06-0793

    Article  PubMed  Google Scholar 

  • Morschhauser J (2010) Regulation of white-opaque switching in Candida albicans. Med Microbiol Immunol 199(3):165–172. doi:10.1007/s00430-010-0147-0

    Article  PubMed  CAS  Google Scholar 

  • Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J, Hofs S, Gratacap RL, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Forster TM, Hebecker B, Kasper L, Vizcay G, Iancu SI, Kichik N, Hader A, Kurzai O, Luo T, Kruger T, Kniemeyer O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B, Naglik JR (2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nat 532(7597):64–68. doi:10.1038/nature17625

    Article  CAS  Google Scholar 

  • Mulhern SM, Logue ME, Butler G (2006) Candida albicans transcription factor Ace2 regulates metabolism and is required for filamentation in hypoxic conditions. Eukaryot Cell 5(12):2001–2013. doi:10.1128/EC.00155-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murad AMA, Leng P, Straffon M, Wishart J, Macaskill S, MacCallum D, Schnell N, Talibi D, Marechal D, Tekaia F, d’Enfert C, Gaillardin C, Odds FC, Brown AJP (2001) NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J 20:4742–4752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nantel A, Dignard D, Bachewich C, Harcus D, Marcil A, Bouin AP, Sensen CW, Hogues H, van het Hoog M, Gordon P, Rigby T, Benoit F, Tessier DC, Thomas DY, Whiteway M (2002) Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition. Mol Biol Cell 13(10):3452–3465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nobile CJ, Nett JE, Andes DR, Mitchell AP (2006) Function of Candida albicans adhesin Hwp1 in biofilm formation. Eukaryot Cell 5(10):1604–1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR, Mitchell AP (2008a) Complementary adhesin function in C. albicans biofilm formation. Curr Biol 18(14):1017–1024. doi:10.1016/j.cub.2008.06.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nobile CJ, Solis N, Myers CL, Fay AJ, Deneault JS, Nantel A, Mitchell AP, Filler SG (2008b) Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions. Cell Microbiol 10(11):2180–2196. doi:10.1111/j.1462-5822.2008.01198.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noble SM, French S, Kohn LA, Chen V, Johnson AD (2010) Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat Genet 42(7):590–598. doi:ng.605 [pii]10.1038/ng.605

  • O’Meara TR, Veri AO, Ketela T, Jiang B, Roemer T, Cowen LE (2015) Global analysis of fungal morphology exposes mechanisms of host cell escape. Nat Commun 6:6741. doi:10.1038/ncomms7741

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Odds FC (1988) Candida and Candidosis, 2nd edn. Baillière Tindall, London

    Google Scholar 

  • Pande K, Chen C, Noble SM (2013) Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. Nat Genet 45(9):1088–1091. doi:10.1038/ng.2710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park HO, Bi E (2007) Central roles of small GTPases in the development of cell polarity in yeast and beyond. Microbiol Mol Biol Rev 71(1):48–96. doi:10.1128/MMBR.00028-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pierce CG, Chaturvedi AK, Lazzell AL, Powell AT, Saville SP, McHardy SF, Lopez-Ribot JL (2015) A novel small molecule inhibitor of biofilm formation, filamentation and virulence with low potential for the development of resistance. NPJ Biofilms Microbiomes 1. doi:10.1038/npjbiofilms.2015.12

  • Porta A, Ramon AM, Fonzi WA (1999) PRR1, a homolog of Aspergillus nidulans palF, controls pH-dependent gene expression and filamentation in Candida albicans. J Bacteriol 181(24):7516–7523

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rikkerink EH, Magee BB, Magee PT (1988) Opaque-white phenotype transition: a programmed morphological transition in Candida albicans. J Bacteriol 170(2):895–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rocha CR, Schroppel 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(11):3631–3643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, Tandia F, Linteau A, Sillaots S, Marta C, Martel N, Veronneau S, Lemieux S, Kauffman S, Becker J, Storms R, Boone C, Bussey H (2003) Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol 50(1):167–181

    Article  CAS  PubMed  Google Scholar 

  • Saputo S, Chabrier-Rosello Y, Luca FC, Kumar A, Krysan DJ (2012) The RAM network in pathogenic fungi. Eukaryot Cell 11(6):708–717. doi:10.1128/EC.00044-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasse C, Hasenberg M, Weyler M, Gunzer M, Morschhauser J (2013) White-opaque switching of Candida albicans allows immune evasion in an environment-dependent fashion. Eukaryot Cell 12(1):50–58. doi:10.1128/EC.00266-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(5):1053–1060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR, Heitman J, Cowen LE (2009) Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol 19(8):621–629. doi:10.1016/j.cub.2009.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shapiro RS, Robbins N, Cowen LE (2011) Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 75(2):213–267. doi:10.1128/MMBR.00045-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinha I, Wang YM, Philp R, Li CR, Yap WH, Wang Y (2007) Cyclin-dependent kinases control septin phosphorylation in Candida albicans hyphal development. Dev Cell 13(3):421–432

    Article  CAS  PubMed  Google Scholar 

  • Slutsky B, Staebell M, Anderson J, Risen L, Pfaller M, Soll DR (1987) “White-opaque transition”. In: A second high-frequency switching system in Candida albicans. J Bacteriol 169(1):189–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soll DR, Morrow B, Srikantha T (1993) High-frequency phenotypic switching in Candida albicans. Trends Genet 9(2):61–65

    Article  CAS  PubMed  Google Scholar 

  • Song Y, Cheon SA, Lee KE, Lee SY, Lee BK, Oh DB, Kang HA, Kim JY (2008) Role of the RAM network in cell polarity and hyphal morphogenesis in Candida albicans. Mol Biol Cell 19(12):5456–5477. doi:10.1091/mbc.E08-03-0272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Staab JF, Bradway SD, Fidel PL, Sundstrom P (1999) Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Sci 283(5407):1535–1538

    Google Scholar 

  • Staib P, Morschhauser J (2007) Chlamydospore formation in Candida albicans and Candida dubliniensis--an enigmatic developmental programme. Mycoses 50(1):1–12. doi:MYC1308 [pii]10.1111/j.1439-0507.2006.01308.x

  • Sudbery PE (2001) The germ tubes of Candida albicans hyphae and pseudohyphae show different patterns of septin ring localization. Mol Microbiol 41(1):19–31. doi:mmi2459 [pii]

    Google Scholar 

  • Sudbery PE (2011) Growth of Candida albicans hyphae. Nat Rev Microbiol 9(10):737–748. doi:10.1038/nrmicro2636

    Article  CAS  PubMed  Google Scholar 

  • Sudbery P, Gow N, Berman J (2004) The distinct morphogenic states of Candida albicans. Trends Microbiol 12(7):317–324

    Article  CAS  PubMed  Google Scholar 

  • Tao L, Du H, Guan G, Dai Y, Nobile CJ, Liang W, Cao C, Zhang Q, Zhong J, Huang G (2014) Discovery of a “white-gray-opaque” tristable phenotypic switching system in Candida albicans: roles of non-genetic diversity in host adaptation. PLoS Biol 12(4):e1001830. doi:10.1371/journal.pbio.1001830

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thompson DS, Carlisle PL, Kadosh D (2011) Coevolution of morphology and virulence in Candida species. Eukaryot Cell 10(9):1173–1182. doi:EC.05085-11 [pii]10.1128/EC.05085-11

  • Umeyama T, Kaneko A, Niimi M, Uehara Y (2006) Repression of CDC28 reduces the expression of the morphology-related transcription factors, Efg1p, Nrg1p, Rbf1p, Rim101p, Fkh2p and Tec1p and induces cell elongation in Candida albicans. Yeast 23(7):537–552. doi:10.1002/yea.1373

    Article  CAS  PubMed  Google Scholar 

  • Uppuluri P, Pierce CG, Thomas DP, Bubeck SS, Saville SP, Lopez-Ribot JL (2010) The transcriptional regulator Nrg1p controls Candida albicans biofilm formation and dispersion. Eukaryot Cell 9(10):1531–1537. doi:EC.00111-10 [pii]10.1128/EC.00111-10

  • Ushinsky SC, Harcus D, Ash J, Dignard D, Marcil A, Morchhauser J, Thomas DY, Whiteway M, Leberer E (2002) CDC42 is required for polarized growth in human pathogen Candida albicans. Eukaryot Cell 1(1):95–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang A, Raniga PP, Lane S, Lu Y, Liu H (2009) Hyphal chain formation in Candida albicans: Cdc28-Hgc1 phosphorylation of Efg1 represses cell separation genes. Mol Cell Biol 29(16):4406–4416. doi:10.1128/MCB.01502-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warenda AJ, Konopka JB (2002) Septin function in Candida albicans morphogenesis. Mol Biol Cell 13(8):2732–2746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yokoyama K, Takeo K (1983) Differences of asymmetrical division between the pseudomycelial and yeast forms of Candida albicans and their effect on multiplication. Arch Microbiol 134(3):251–253

    Article  CAS  PubMed  Google Scholar 

  • Yuan X, Mitchell BM, Hua X, Davis DA, Wilhelmus KR (2010) The RIM101 signal transduction pathway regulates Candida albicans virulence during experimental keratomycosis. Invest Ophthalmol Vis Sci 51(9):4668–4676. doi:10.1167/iovs.09-4726

    Article  PubMed  PubMed Central  Google Scholar 

  • Zeidler U, Lettner T, Lassnig C, Muller 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(1):126–142. doi:FYR459 [pii]10.1111/j.1567-1364.2008.00459.x

  • Zheng X, Wang Y, Wang Y (2004) Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis. EMBO J 23(8):1845–1856

    Google Scholar 

  • Zheng XD, Lee RT, Wang YM, Lin QS, Wang Y (2007) Phosphorylation of Rga2, a Cdc42 GAP, by CDK/Hgc1 is crucial for Candida albicans hyphal growth. EMBO J 26(16):3760–3769

    Google Scholar 

  • Zink S, Nass T, Rosen P, Ernst JF (1996) Migration of the fungal pathogen Candida albicans across endothelial monolayers. Infect Immun 64(12):5085–5091

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(10):e256. doi:10.1371/journal.pbio.0050256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

This work was supported by National Institutes of Health grants 5R01AI083344 and 1R21AI117299 in addition to a Voelcker Young Investigator Award from the Max and Minnie Tomerlin Voelcker Fund. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.

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Kadosh, D. (2017). Morphogenesis in C. albicans . In: Prasad, R. (eds) Candida albicans: Cellular and Molecular Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-50409-4_4

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