Skip to main content

From Genes to Networks: The Regulatory Circuitry Controlling Candida albicans Morphogenesis

  • Chapter
  • First Online:
Fungal Physiology and Immunopathogenesis

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 422))

Abstract

Candida albicans is a commensal yeast of most healthy individuals, but also one of the most prevalent human fungal pathogens. During adaptation to the mammalian host, C. albicans encounters different niches where it is exposed to several types of stress, including oxidative, nitrosative (e.g., immune system), osmotic (e.g., kidney and oral cavity) stresses and pH variation (e.g., gastrointestinal (GI) tract and vagina). C. albicans has developed the capacity to respond to the environmental changes by modifying its morphology, which comprises the yeast-to-hypha transition, white-opaque switching, and chlamydospore formation. The yeast-to-hypha transition has been very well characterized and was shown to be modulated by several external stimuli that mimic the host environment. For instance, temperature above 37 ℃, serum, alkaline pH, and CO2 concentration are all reported to enhance filamentation. The transition is characterized by the activation of an intricate regulatory network of signaling pathways, involving many transcription factors. The regulatory pathways that control either the stress response or morphogenesis are required for full virulence and promote survival of C. albicans in the host. Many of these transcriptional circuitries have been characterized, highlighting the complexity and the interconnections between the different pathways. Here, we present the major signaling pathways and the main transcription factors involved in the yeast-to-hypha transition. Furthermore, we describe the role of heat shock transcription factors in the morphogenetic transition, providing an edifying example of the complex cross talk between pathways involved in morphogenesis and stress response.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alex LA, Borkovich KA, Simon MI (1996) Hyphal development in Neurospora crassa: involvement of a two-component histidine kinase. Proc Natl Acad Sci U S A 93(8):3416–3421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alex LA, Korch C, Selitrennikoff CP, Simon MI (1998) COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans. Proc Natl Acad Sci U S A 95(12):7069–7073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almeida RS, Brunke S, Albrecht A, Thewes S, Laue M, Edwards JE et al (2008) The hyphal-associated adhesin and invasin Als3 of Candida albicans mediates iron acquisition from host ferritin. PLoS Pathog 4(11):e1000217

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alonso-Monge R, Navarro-Garcia F, Molero G, Diez-Orejas R, Gustin M, Pla J et al (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 

  • Alonso-Monge R, Real E, Wojda I, Bebelman JP, Mager WH, Siderius M (2001) Hyperosmotic stress response and regulation of cell wall integrity in Saccharomyces cerevisiae share common functional aspects. Mol Microbiol 41(3):717–730

    Article  CAS  PubMed  Google Scholar 

  • Alonso-Monge R, Navarro-Garcia F, Roman E, Negredo AI, Eisman B, Nombela C et al (2003) The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans. Eukaryot Cell 2(2):351–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alspaugh JA, Cavallo LM, Perfect JR, Heitman J (2000) RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Mol Microbiol 36(2):352–365

    Article  CAS  PubMed  Google Scholar 

  • Arana DM, Nombela C, Alonso-Monge R, Pla J (2005) The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans. Microbiology 151(Pt 4):1033–1049

    Article  CAS  PubMed  Google Scholar 

  • Baek YU, Martin SJ, Davis DA (2006) Evidence for novel pH-dependent regulation of Candida albicans Rim101, a direct transcriptional repressor of the cell wall beta-glycosidase Phr2. Eukaryot Cell 5(9):1550–1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bahn YS, 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(2):391–409

    Article  CAS  PubMed  Google Scholar 

  • Baker H, Sidorowicz A, Sehgal SN, Vezina C (1978) Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation. J Antibiot (Tokyo) 31(6):539–45

    Article  CAS  PubMed  Google Scholar 

  • Banerjee M, Thompson DS, Lazzell A, Carlisle PL, Pierce C, Monteagudo C et al (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 

  • Bardwell L, Cook JG, Voora D, Baggott DM, Martinez AR, Thorner J (1998a) Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK. Genes Dev 12(18):2887–2898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bardwell L, Cook JG, Zhu-Shimoni JX, Voora D, Thorner J (1998b) Differential regulation of transcription: repression by unactivated mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 proteins. Proc Natl Acad Sci U S A 95(26):15400–15405

    Article  CAS  PubMed  PubMed Central  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

    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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Basso V, Znaidi S, Lagage V, Cabral V, Schoenherr F, LeibundGut-Landmann S et al (2017) The two-component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis-induced ROS accumulation. Mol Microbiol 106(1):157–182

    Article  CAS  PubMed  Google Scholar 

  • Bastidas RJ, Heitman J, Cardenas ME (2009) The protein kinase Tor1 regulates adhesin gene expression in Candida albicans. PLoS Pathog 5(2):e1000294

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bauer J, Wendland J (2007) Candida albicans Sfl1 suppresses flocculation and filamentation. Eukaryot Cell 6(10):1736–1744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bendel CM, Hess DJ, Garni RM, Henry-Stanley M, Wells CL (2003) Comparative virulence of Candida albicans yeast and filamentous forms in orally and intravenously inoculated mice. Crit Care Med 31(2):501–507

    Article  PubMed  Google Scholar 

  • Bidlingmaier S, Weiss EL, Seidel C, Drubin DG, Snyder M (2001) The Cbk1p pathway is important for polarized cell growth and cell separation in Saccharomyces cerevisiae. Mol Cell Biol 21(7):2449–2462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birse CE, Irwin MY, Fonzi WA, Sypherd PS (1993) Cloning and characterization of ECE1, a gene expressed in association with cell elongation of the dimorphic pathogen Candida albicans. Infect Immun 61(9):3648–3655

    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

    Article  CAS  PubMed  Google Scholar 

  • 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(2):348–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Borg M, Ruchel R (1988) Expression of extracellular acid proteinase by proteolytic Candida spp. during experimental infection of oral mucosa. Infect Immun 56(3):626–31

    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, Johnson AD (2000) TUP1, CPH1 and EFG1 make independent contributions to filamentation in Candida albicans. Genetics 155(1):57–67

    CAS  PubMed  PubMed Central  Google Scholar 

  • Broach JR (2012) Nutritional control of growth and development in yeast. Genetics 192(1):73–105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brown AJ, Gow NA (1999) Regulatory networks controlling Candida albicans morphogenesis. Trends Microbiol 7(8):333–338

    Article  CAS  PubMed  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 

  • Buffo J, Herman MA, Soll DR (1984) A characterization of pH-regulated dimorphism in Candida albicans. Mycopathologia 85(1–2):21–30

    Article  CAS  PubMed  Google Scholar 

  • Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S, Munro CA et al (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459(7247):657–662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calderon-Norena DM, Gonzalez-Novo A, Orellana-Munoz S, Gutierrez-Escribano P, Arnaiz-Pita Y, Duenas-Santero E et al (2015) A single nucleotide polymorphism uncovers a novel function for the transcription factor Ace2 during Candida albicans hyphal development. PLoS Genet 11(4):e1005152

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Calera JA, Calderone R (1999) Flocculation of hyphae is associated with a deletion in the putative CaHK1 two-component histidine kinase gene from Candida albicans. Microbiology 145(Pt 6):1431–1442

    Article  CAS  PubMed  Google Scholar 

  • Calera JA, Zhao XJ, De Bernardis F, Sheridan M, Calderone R (1999) Avirulence of Candida albicans CaHK1 mutants in a murine model of hematogenously disseminated candidiasis. Infect Immun 67(8):4280–4284

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cao YY, Cao YB, Xu Z, Ying K, Li Y, Xie Y et al (2005) cDNA microarray analysis of differential gene expression in Candida albicans biofilm exposed to farnesol. Antimicrob Agents Chemother 49(2):584–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao F, Lane S, Raniga PP, Lu Y, Zhou Z, Ramon K et al (2006) The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans. Mol Biol Cell 17(1):295–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao C, Wu M, Bing J, Tao L, Ding X, Liu X et al (2017) Global regulatory roles of the cAMP/PKA pathway revealed by phenotypic, transcriptomic and phosphoproteomic analyses in a null mutant of the PKA catalytic subunit in Candida albicans. Mol Microbiol 105(1):46–64

    Article  CAS  PubMed  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 U S A 106(2):599–604

    Article  CAS  PubMed  Google Scholar 

  • Chauhan NM, Shinde RB, Karuppayil SM (2013) Effect of alcohols on filamentation, growth, viability and biofilm development in Candida albicans. Braz J Microbiol 44(4):1315–1320

    Article  PubMed  Google Scholar 

  • Chauvel M, Nesseir A, Cabral V, Znaidi S, Goyard S, Bachellier-Bassi S et al (2012) A versatile overexpression strategy in the pathogenic yeast Candida albicans: identification of regulators of morphogenesis and fitness. PLoS ONE 7(9):e45912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Fujita M, Feng Q, Clardy J, Fink GR (2004) Tyrosol is a quorum-sensing molecule in Candida albicans. Proc Natl Acad Sci U S A 101(14):5048–5052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chou S, Lane S, Liu H (2006) Regulation of mating and filamentation genes by two distinct Ste12 complexes in Saccharomyces cerevisiae. Mol Cell Biol 26(13):4794–4805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Citiulo F, Jacobsen ID, Miramon P, Schild L, Brunke S, Zipfel P et al (2012) Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLoS Pathog 8(6):e1002777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cleary IA, Mulabagal P, Reinhard SM, Yadev NP, Murdoch C, Thornhill MH et al (2010) Pseudohyphal regulation by the transcription factor Rfg1p in Candida albicans. Eukaryot Cell 9(9):1363–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clemente-Blanco A, Gonzalez-Novo A, Machin F, Caballero-Lima D, Aragon L, Sanchez M et al (2006) The Cdc14p phosphatase affects late cell-cycle events and morphogenesis in Candida albicans. J Cell Sci 119(Pt 6):1130–1143

    Article  CAS  PubMed  Google Scholar 

  • Colman-Lerner A, Chin TE, Brent R (2001) Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates. Cell 107(6):739–750

    Article  CAS  PubMed  Google Scholar 

  • Colombo S, Ma P, Cauwenberg L, Winderickx J, Crauwels M, Teunissen A et al (1998) Involvement of distinct G-proteins, Gpa2 and Ras, in glucose- and intracellular acidification-induced cAMP signalling in the yeast Saccharomyces cerevisiae. EMBO J 17(12):3326–3341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colombo S, Ronchetti D, Thevelein JM, Winderickx J, Martegani E (2004) Activation state of the Ras2 protein and glucose-induced signaling in Saccharomyces cerevisiae. J Biol Chem 279(45):46715–46722

    Article  CAS  PubMed  Google Scholar 

  • Colombo S, Broggi S, Collini M, D’Alfonso L, Chirico G, Martegani E (2017) Detection of cAMP and of PKA activity in Saccharomyces cerevisiae single cells using Fluorescence Resonance Energy Transfer (FRET) probes. Biochem Biophys Res Commun 487(3):594–599

    Article  CAS  PubMed  Google Scholar 

  • Conlan RS, Tzamarias D (2001) Sfl1 functions via the co-repressor Ssn6-Tup1 and the cAMP-dependent protein kinase Tpk2. J Mol Biol 309(5):1007–1015

    Article  CAS  PubMed  Google Scholar 

  • Cook JG, Bardwell L, Kron SJ, Thorner J (1996) Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae. Genes Dev 10(22):2831–2848

    Article  CAS  PubMed  Google Scholar 

  • Cornet M, Bidard F, Schwarz P, Da Costa G, Blanchin-Roland S, Dromer F et al (2005) Deletions of endocytic components VPS28 and VPS32 affect growth at alkaline pH and virulence through both RIM101-dependent and RIM101-independent pathways in Candida albicans. Infect Immun 73(12):7977–7987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Correia I, Alonso-Monge R, Pla J (2017) Corrigendum: the Hog1 MAP kinase promotes the recovery from cell cycle arrest induced by hydrogen peroxide in Candida albicans. Front Microbiol 8:555

    Article  PubMed  PubMed Central  Google Scholar 

  • Csank C, Schroppel K, Leberer E, Harcus D, Mohamed O, Meloche S et al (1998) Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis. Infect Immun 66(6):2713–2721

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cullen PJ, Sprague GF Jr (2012) The regulation of filamentous growth in yeast. Genetics 190(1):23–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cullen PJ, Schultz J, Horecka J, Stevenson BJ, Jigami Y, Sprague GF Jr (2000) Defects in protein glycosylation cause SHO1-dependent activation of a STE12 signaling pathway in yeast. Genetics 155(3):1005–1018

    CAS  PubMed  PubMed Central  Google Scholar 

  • Davis-Hanna A, Piispanen AE, Stateva LI, Hogan DA (2008) Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis. Mol Microbiol 67(1):47–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de la Torre-Ruiz MA, Mozo-Villarias 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(8):669–679

    Article  PubMed  Google Scholar 

  • de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3(8):735–740

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Nadal E, Real FX, Posas F (2007) Mucins, osmosensors in eukaryotic cells? Trends Cell Biol 17(12):571–574

    Article  PubMed  CAS  Google Scholar 

  • DeRisi JL, Iyer VR, Brown PO (1997) Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278(5338):680–686

    Article  CAS  PubMed  Google Scholar 

  • Desai PR, van Wijlick L, Kurtz D, Juchimiuk M, Ernst JF (2015) Hypoxia and Temperature Regulated Morphogenesis in Candida albicans. PLoS Genet 11(8):e1005447

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Doedt T, Krishnamurthy S, Bockmuhl DP, Tebarth B, Stempel C, Russell CL et al (2004) APSES proteins regulate morphogenesis and metabolism in Candida albicans. Mol Biol Cell 15(7):3167–3180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du LL, Novick P (2002) Pag1p, a novel protein associated with protein kinase Cbk1p, is required for cell morphogenesis and proliferation in Saccharomyces cerevisiae. Mol Biol Cell 13(2):503–514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du C, Calderone R, Richert J, Li D (2005) Deletion of the SSK1 response regulator gene in Candida albicans contributes to enhanced killing by human polymorphonuclear neutrophils. Infect Immun 73(2):865–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eckert SE, Heinz WJ, Zakikhany K, Thewes S, Haynes K, Hube B et al (2007) PGA4, a GAS homologue from Candida albicans, is up-regulated early in infection processes. Fungal Genet Biol 44(5):368–377

    Article  CAS  PubMed  Google Scholar 

  • Eisman B, Alonso-Monge R, Roman E, Arana D, Nombela C, Pla J (2006) 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 5(2):347–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elion EA (2000) Pheromone response, mating and cell biology. Curr Opin Microbiol 3(6):573–581

    Article  CAS  PubMed  Google Scholar 

  • Enjalbert B, Nantel A, Whiteway M (2003) Stress-induced gene expression in Candida albicans: absence of a general stress response. Mol Biol Cell 14(4):1460–1467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ernst JF (2000) Regulation of dimorphism in Candida albicans. Contrib Microbiol 5:98–111

    Article  CAS  PubMed  Google Scholar 

  • Erwig LP, Gow NA (2016) Interactions of fungal pathogens with phagocytes. Nat Rev Microbiol 14(3):163–176

    Article  CAS  PubMed  Google Scholar 

  • Fan Y, He H, Dong Y, Pan H (2013) Hyphae-specific genes HGC1, ALS3, HWP1, and ECE1 and relevant signaling pathways in Candida albicans. Mycopathologia 176(5–6):329–335

    Article  CAS  PubMed  Google Scholar 

  • 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(2):484–496

    Article  CAS  PubMed  Google Scholar 

  • Fassler JS, West AH (2011) Fungal Skn7 stress responses and their relationship to virulence. Eukaryot Cell 10(2):156–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng Q, Summers E, Guo B, Fink G (1999) Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J Bacteriol 181(20):6339–6346

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandes M, Xiao H, Lis JT (1995) Binding of heat shock factor to and transcriptional activation of heat shock genes in Drosophila. Nucleic Acids Res 23(23):4799–4804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fonzi WA (1999) PHR1 and PHR2 of Candida albicans encode putative glycosidases required for proper cross-linking of beta-1,3- and beta-1,6-glucans. J Bacteriol 181(22):7070–7079

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fradin C, De Groot P, MacCallum D, Schaller M, Klis F, Odds FC et al (2005) Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood. Mol Microbiol 56(2):397–415

    Article  CAS  PubMed  Google Scholar 

  • Fujita A, Kikuchi Y, Kuhara S, Misumi Y, Matsumoto S, Kobayashi H (1989) Domains of the SFL1 protein of yeasts are homologous to Myc oncoproteins or yeast heat-shock transcription factor. Gene 85(2):321–328

    Article  CAS  PubMed  Google Scholar 

  • Fujita A, Tonouchi A, Hiroko T, Inose F, Nagashima T, Satoh R et al (1999) Hsl7p, a negative regulator of Ste20p protein kinase in the Saccharomyces cerevisiae filamentous growth-signaling pathway. Proc Natl Acad Sci U S A 96(15):8522–8527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuller KK, Rhodes JC (2012) Protein kinase A and fungal virulence: a sinister side to a conserved nutrient sensing pathway. Virulence 3(2):109–121

    Article  PubMed  PubMed Central  Google Scholar 

  • Galeote VA, Alexandre H, Bach B, Delobel P, Dequin S, Blondin B (2007) Sfl1p acts as an activator of the HSP30 gene in Saccharomyces cerevisiae. Curr Genet 52(2):55–63

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Rodriguez LJ, Valle R, Duran A, Roncero C (2005) Cell integrity signaling activation in response to hyperosmotic shock in yeast. FEBS Lett 579(27):6186–6190

    Article  CAS  PubMed  Google Scholar 

  • Giacometti R, Kronberg F, Biondi RM, Passeron S (2009) Catalytic isoforms Tpk1 and Tpk2 of Candida albicans PKA have non-redundant roles in stress response and glycogen storage. Yeast 26(5):273–285

    Article  CAS  PubMed  Google Scholar 

  • Giusani AD, Vinces M, Kumamoto CA (2002) Invasive filamentous growth of Candida albicans is promoted by Czf1p-dependent relief of Efg1p-mediated repression. Genetics 160(4):1749–1753

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Gow NA, Brown AJ, Odds FC (2002) Fungal morphogenesis and host invasion. Curr Opin Microbiol 5(4):366–371

    Article  CAS  PubMed  Google Scholar 

  • Grubb SE, Murdoch C, Sudbery PE, Saville SP, Lopez-Ribot JL, Thornhill MH (2009) Adhesion of Candida albicans to endothelial cells under physiological conditions of flow. Infect Immun 77(9):3872–3878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hall RA, Turner KJ, Chaloupka J, Cottier F, De Sordi L, Sanglard D et al (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harashima T, Heitman J (2005) G subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae. Mol Biol Cell 16(10):4557–4571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helliwell SB, Howald I, Barbet N, Hall MN (1998) TOR2 is part of two related signaling pathways coordinating cell growth in Saccharomyces cerevisiae. Genetics 148(1):99–112

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hiller E, Zavrel M, Hauser N, Sohn K, Burger-Kentischer A, Lemuth K et al (2011) Adaptation, adhesion and invasion during interaction of Candida albicans with the host–focus on the function of cell wall proteins. Int J Med Microbiol 301(5):384–389

    Article  CAS  PubMed  Google Scholar 

  • 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(5):e1000889

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hnisz D, Bardet AF, Nobile CJ, Petryshyn A, Glaser W, Schock U et al (2012) A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis. PLoS Genet 8(12):e1003118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hogan DA, Sundstrom P (2009) The Ras/cAMP/PKA signaling pathway and virulence in Candida albicans. Future Microbiol. 4(10):1263–1270

    Article  CAS  PubMed  Google Scholar 

  • Hogan DA, Vik A, Kolter R (2004) A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology. Mol Microbiol 54(5):1212–1223

    Article  CAS  PubMed  Google Scholar 

  • Hohmann S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66(2):300–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hohmann S (2009) Control of high osmolarity signalling in the yeast Saccharomyces cerevisiae. FEBS Lett 583(24):4025–4029

    Article  CAS  PubMed  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

    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

    Article  CAS  PubMed  Google Scholar 

  • Hornby JM, Kebaara BW, Nickerson KW (2003) Farnesol biosynthesis in Candida albicans: cellular response to sterol inhibition by zaragozic acid B. Antimicrob Agents Chemother 47(7):2366–2369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoyer LL, Cieslinski LB, McLaughlin MM, Torphy TJ, Shatzman AR, Livi GP (1994) A Candida albicans cyclic nucleotide phosphodiesterase: cloning and expression in Saccharomyces cerevisiae and biochemical characterization of the recombinant enzyme. Microbiology 140(Pt 7):1533–1542

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Liu E, Bai X, Zhang A (2010) The localization and concentration of the PDE2-encoded high-affinity cAMP phosphodiesterase is regulated by cAMP-dependent protein kinase A in the yeast Saccharomyces cerevisiae. FEMS Yeast Res 10(2):177–187

    Article  CAS  PubMed  Google Scholar 

  • Hube B, Monod M, Schofield DA, Brown AJ, Gow NA (1994) Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans. Mol Microbiol 14(1):87–99

    Article  CAS  PubMed  Google Scholar 

  • Hwang CS, Oh JH, Huh WK, Yim HS, Kang SO (2003) Ssn6, an important factor of morphological conversion and virulence in Candida albicans. Mol Microbiol 47(4):1029–1043

    Article  CAS  PubMed  Google Scholar 

  • Jarosz DF, Taipale M, Lindquist S (2010) Protein homeostasis and the phenotypic manifestation of genetic diversity: principles and mechanisms. Annu Rev Genet 44:189–216

    Article  CAS  PubMed  Google Scholar 

  • Jenull S, Tscherner M, Gulati M, Nobile CJ, Chauhan N, Kuchler K (2017) The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals. Sci Rep 7(1):8308

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jung WH, Stateva LI (2003) The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans. Microbiology 149(Pt 10):2961–2976

    Article  CAS  PubMed  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 

  • Keleher CA, Redd MJ, Schultz J, Carlson M, Johnson AD (1992) Ssn6-Tup1 is a general repressor of transcription in yeast. Cell 68(4):709–719

    Article  CAS  PubMed  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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim TS, Lee SB, Kang HS (2004) Glucose repression of STA1 expression is mediated by the Nrg1 and Sfl1 repressors and the Srb8-11 complex. Mol Cell Biol 24(17):7695–7706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klengel T, Liang WJ, Chaloupka J, Ruoff C, Schroppel K, Naglik JR et al (2005) Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr Biol 15(22):2021–2026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi O, Suda H, Ohtani T, Sone H (1996) Molecular cloning and analysis of the dominant flocculation gene FLO8 from Saccharomyces cerevisiae. Mol Gen Genet 251(6):707–715

    CAS  PubMed  Google Scholar 

  • Kraakman L, Lemaire K, Ma P, Teunissen AW, Donaton MC, Van Dijck P et al (1999) A Saccharomyces cerevisiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose. Mol Microbiol 32(5):1002–1012

    Article  CAS  PubMed  Google Scholar 

  • Kruppa M, Jabra-Rizk MA, Meiller TF, Calderone R (2004) The histidine kinases of Candida albicans: regulation of cell wall mannan biosynthesis. FEMS Yeast Res 4(4–5):409–416

    Article  CAS  PubMed  Google Scholar 

  • Kubler E, Mosch HU, Rupp S, Lisanti MP (1997) Gpa2p, a G-protein alpha-subunit, regulates growth and pseudohyphal development in Saccharomyces cerevisiae via a cAMP-dependent mechanism. J Biol Chem 272(33):20321–20323

    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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kullberg BJ, Arendrup MC (2016) Invasive candidiasis. N Engl J Med 374(8):794–795

    PubMed  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 (2008) Molecular mechanisms of mechanosensing and their roles in fungal contact sensing. Nat Rev Microbiol 6(9):667–673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumamoto CA, Vinces MD (2005) Alternative Candida albicans lifestyles: growth on surfaces. Annu Rev Microbiol 59:113–133

    Article  CAS  PubMed  Google Scholar 

  • Kunz J, Henriquez R, Schneider U, Deuter-Reinhard M, Movva NR, Hall MN (1993) Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73(3):585–596

    Article  CAS  PubMed  Google Scholar 

  • Lane S, Birse C, Zhou S, Matson R, Liu H (2001a) DNA array studies demonstrate convergent regulation of virulence factors by Cph1, Cph2, and Efg1 in Candida albicans. J Biol Chem 276(52):48988–48996

    Article  CAS  PubMed  Google Scholar 

  • Lane S, Zhou S, Pan T, Dai Q, Liu H (2001b) The basic helix-loop-helix transcription factor Cph2 regulates hyphal development in Candida albicans partly via TEC1. Mol Cell Biol 21(19):6418–6428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lassak T, Schneider E, Bussmann M, Kurtz D, Manak JR, Srikantha T et al (2011) Target specificity of the Candida albicans Efg1 regulator. Mol Microbiol 82(3):602–618

    Article  CAS  PubMed  Google Scholar 

  • Leach MD, Tyc KM, Brown AJ, Klipp E (2012) Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans. PLoS ONE 7(3):e32467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leach MD, Farrer RA, Tank K, Miao Z, Walker LA, Cuomo CA et al (2016) Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans. Nat Commun. 26(7):11704

    Article  CAS  Google Scholar 

  • Leberer E, Harcus D, Broadbent ID, Clark KL, Dignard D, Ziegelbauer K et al (1996) Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. Proc Natl Acad Sci U S A 93(23):13217–13222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leberer E, Harcus D, Dignard D, Johnson L, Ushinsky S, Thomas DY et al (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 

  • Lee BN, Elion EA (1999) The MAPKKK Ste11 regulates vegetative growth through a kinase cascade of shared signaling components. Proc Natl Acad Sci U S A 96(22):12679–12684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JE, Oh JH, Ku M, Kim J, Lee JS, Kang SO (2015) Ssn6 has dual roles in Candida albicans filament development through the interaction with Rpd31. FEBS Lett 589(4):513–520

    Article  CAS  PubMed  Google Scholar 

  • Levin DE (2005) Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 69(2):262–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li D, Gurkovska V, Sheridan M, Calderone R, Chauhan N (2004a) Studies on the regulation of the two-component histidine kinase gene CHK1 in Candida albicans using the heterologous lacZ reporter gene. Microbiology 150(Pt 10):3305–3313

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Su C, Mao X, Cao F, Chen J (2007) Roles of Candida albicans Sfl1 in hyphal development. Eukaryot Cell 6(11):2112–2121

    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. Science 266(5191):1723–1726

    Article  CAS  PubMed  Google Scholar 

  • Liu W, Zhao J, Li X, Li Y, Jiang L (2010) The protein kinase CaSch9p is required for the cell growth, filamentation and virulence in the human fungal pathogen Candida albicans. FEMS Yeast Res 10(4):462–470

    Article  CAS  PubMed  Google Scholar 

  • Lo WS, Dranginis AM (1998) The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae. Mol Biol Cell 9(1):161–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lo HJ, Kohler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR (1997) Nonfilamentous C. albicans mutants are avirulent. Cell 90(5):939–49

    Article  CAS  PubMed  Google Scholar 

  • Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D et al (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10(3):457–468

    Article  CAS  PubMed  Google Scholar 

  • Lorenz MC, Heitman J (1997) Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog. EMBO J 16(23):7008–7018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lorenz MC, Pan X, Harashima T, Cardenas ME, Xue Y, Hirsch JP et al (2000) The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Genetics 154(2):609–622

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lorenz MC, Bender JA, Fink GR (2004) Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3(5):1076–1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y, Su C, Mao X, Raniga PP, Liu H, Chen J (2008) Efg1-mediated recruitment of NuA4 to promoters is required for hypha-specific Swi/Snf binding and activation in Candida albicans. Mol Biol Cell 19(10):4260–4272

    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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y, Su C, Liu H (2014) Candida albicans hyphal initiation and elongation. Trends Microbiol 22(12):707–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma P, Wera S, Van Dijck P, Thevelein JM (1999) The PDE1-encoded low-affinity phosphodiesterase in the yeast Saccharomyces cerevisiae has a specific function in controlling agonist-induced cAMP signaling. Mol Biol Cell 10(1):91–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacIsaac KD, Wang T, Gordon DB, Gifford DK, Stormo GD, Fraenkel E (2006) An improved map of conserved regulatory sites for Saccharomyces cerevisiae. BMC Bioinformatics 7:113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Madhani HD, Fink GR (1997) Combinatorial control required for the specificity of yeast MAPK signaling. Science 275(5304):1314–1317

    Article  CAS  PubMed  Google Scholar 

  • Madhani HD, Styles CA, Fink GR (1997) MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation. Cell 91(5):673–684

    Article  CAS  PubMed  Google Scholar 

  • Maeda T, Takekawa M, Saito H (1995) Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science 269(5223):554–558

    Article  CAS  PubMed  Google Scholar 

  • Magee BB, Legrand M, Alarco AM, Raymond M, Magee PT (2002) Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans. Mol Microbiol 46(5):1345–1351

    Article  CAS  PubMed  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

    Article  CAS  PubMed  Google Scholar 

  • Mao X, Cao F, Nie X, Liu H, Chen J (2006) The Swi/Snf chromatin remodeling complex is essential for hyphal development in Candida albicans. FEBS Lett 580(11):2615–2622

    Article  CAS  PubMed  Google Scholar 

  • Marcil A, Harcus D, Thomas DY, Whiteway M. Candida albicans killing by RAW 264.7 mouse macrophage cells: effects of Candida genotype, infection ratios, and gamma interferon treatment. Infect Immun. 2002;70(11):6319–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin R, Moran GP, Jacobsen ID, Heyken A, Domey J, Sullivan DJ et al (2011) The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension. PLoS ONE 6(4):e18394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(2):555–562

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mazanka E, Alexander J, Yeh BJ, Charoenpong P, Lowery DM, Yaffe M et al (2008) The NDR/LATS family kinase Cbk1 directly controls transcriptional asymmetry. PLoS Biol 6(8):e203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McNemar MD, Fonzi WA (2002) Conserved serine/threonine kinase encoded by CBK1 regulates expression of several hypha-associated transcripts and genes encoding cell wall proteins in Candida albicans. J Bacteriol 184(7):2058–2061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mendelsohn S, Pinsky M, Weissman Z, Kornitzer D (2017) Regulation of the Candida albicans hypha-inducing transcription factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1. mSpehe 2(2):e00248-16

    Google Scholar 

  • Messenguy F, Vierendeels F, Scherens B, Dubois E (2000) In Saccharomyces cerevisiae, expression of arginine catabolic genes CAR1 and CAR2 in response to exogenous nitrogen availability is mediated by the Ume6 (CargRI)-Sin3 (CargRII)-Rpd3 (CargRIII) complex. J Bacteriol 182(11):3158–3164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minato T, Wang J, Akasaka K, Okada T, Suzuki N, Kataoka T (1994) Quantitative analysis of mutually competitive binding of human Raf-1 and yeast adenylyl cyclase to Ras proteins. J Biol Chem 269(33):20845–20851

    CAS  PubMed  Google Scholar 

  • Miwa T, Takagi Y, Shinozaki M, Yun CW, Schell WA, Perfect JR et al (2004) Gpr1, a putative G-protein-coupled receptor, regulates morphogenesis and hypha formation in the pathogenic fungus Candida albicans. Eukaryot Cell 3(4):919–931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monge RA, Roman E, Nombela C, Pla J (2006) The MAP kinase signal transduction network in Candida albicans. Microbiology 152(Pt 4):905–912

    Article  CAS  PubMed  Google Scholar 

  • Morozov AV, Siggia ED (2007) Connecting protein structure with predictions of regulatory sites. Proc Natl Acad Sci U S A 104(17):7068–7073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J et al (2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532(7597):64–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muhlschlegel FA, Fonzi WA (1997) PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression. Mol Cell Biol 17(10):5960–5967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukaremera L, Lee KK, Mora-Montes HM, Gow NAR (2017) Candida albicans yeast, pseudohyphal, and hyphal morphogenesis differentially affects immune recognition. Front Immunol 8:629

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murad AM, Leng P, Straffon M, Wishart J, Macaskill S, MacCallum D et al (2001) NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J 20(17):4742–4752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagahashi S, Mio T, Ono N, Yamada-Okabe T, Arisawa M, Bussey H et al (1998) Isolation of CaSLN1 and CaNIK1, the genes for osmosensing histidine kinase homologues, from the pathogenic fungus Candida albicans. Microbiology 144(Pt 2):425–432

    Article  CAS  PubMed  Google Scholar 

  • Nair R, Shariq M, Dhamgaye S, Mukhopadhyay CK, Shaikh S, Prasad R (2017) Non-heat shock responsive roles of HSF1 in Candida albicans are essential under iron deprivation and drug defense. Biochim Biophys Acta 1864(2):345–354

    Article  CAS  Google Scholar 

  • Nantel A, Dignard D, Bachewich C, Harcus D, Marcil A, Bouin AP et al (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 

  • Naseem S, Araya E, Konopka JB (2015) Hyphal growth in Candida albicans does not require induction of hyphal-specific gene expression. Mol Biol Cell 26(6):1174–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Navarro-Garcia F, Sanchez M, Pla J, Nombela C (1995) Functional characterization of the MKC1 gene of Candida albicans, which encodes a mitogen-activated protein kinase homolog related to cell integrity. Mol Cell Biol 15(4):2197–2206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Navarro-Garcia F, Alonso-Monge R, Rico H, Pla J, Sentandreu R, Nombela C (1998) A role for the MAP kinase gene MKC1 in cell wall construction and morphological transitions in Candida albicans. Microbiology 144(Pt 2):411–424

    Article  CAS  PubMed  Google Scholar 

  • Nelson B, Kurischko C, Horecka J, Mody M, Nair P, Pratt L et al (2003) RAM: a conserved signaling network that regulates Ace2p transcriptional activity and polarized morphogenesis. Mol Biol Cell 14(9):3782–3803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nemecek JC, Wuthrich M, Klein BS (2006) Global control of dimorphism and virulence in fungi. Science 312(5773):583–588

    Article  CAS  PubMed  Google Scholar 

  • Nicholls S, Leach MD, Priest CL, Brown AJ (2009) Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals. Mol Microbiol 74(4):844–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicholls S, MacCallum DM, Kaffarnik FA, Selway L, Peck SC, Brown AJ (2011) Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans. Fungal Genet Biol 48(3):297–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nobile CJ, Mitchell AP (2005) Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p. Curr Biol 15(12):1150–5

    Article  CAS  PubMed  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Odds FC (1987) Candida infections: an overview. Crit Rev Microbiol 15(1):1–5

    Article  CAS  PubMed  Google Scholar 

  • Odds FC (1988) Candida and Candidosis: a review and bibliography, 2nd edn

    Google Scholar 

  • Ollert MW, Sohnchen R, Korting HC, Ollert U, Brautigam S, Brautigam W (1993) Mechanisms of adherence of Candida albicans to cultured human epidermal keratinocytes. Infect Immun 61(11):4560–4568

    CAS  PubMed  PubMed Central  Google Scholar 

  • O’Meara TR, Robbins N, Cowen LE (2017) The Hsp90 chaperone network modulates Candida virulence traits. Trends Microbiol 25(10):809–819

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • O’Rourke SM, Herskowitz I (1998) The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev 12(18):2874–2886

    Article  PubMed  PubMed Central  Google Scholar 

  • Palecek SP, Parikh AS, Kron SJ (2002) Sensing, signalling and integrating physical processes during Saccharomyces cerevisiae invasive and filamentous growth. Microbiology 148(Pt 4):893–907

    Article  CAS  PubMed  Google Scholar 

  • Pan X, Heitman J (1999) Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol Cell Biol 19(7):4874–4887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pan X, Heitman J (2002) Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation. Mol Cell Biol 22(12):3981–3993

    Article  CAS  PubMed  PubMed Central  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paravicini G, Mendoza A, Antonsson B, Cooper M, Losberger C, Payton MA (1996) The Candida albicans PKC1 gene encodes a protein kinase C homolog necessary for cellular integrity but not dimorphism. Yeast 12(8):741–756

    Article  CAS  PubMed  Google Scholar 

  • Parrino SM, Si H, Naseem S, Groudan K, Gardin J, Konopka JB (2017) cAMP-independent signal pathways stimulate hyphal morphogenesis in Candida albicans. Mol Microbiol 103(5):764–779

    Article  CAS  PubMed  Google Scholar 

  • Penalva MA, Arst HN, Jr (2002) Regulation of gene expression by ambient pH in filamentous fungi and yeasts. Microbiol Mol Biol Rev 66(3):426–46 (table of contents)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez JC, Kumamoto CA, Johnson AD (2013) Candida albicans commensalism and pathogenicity are intertwined traits directed by a tightly knit transcriptional regulatory circuit. PLoS Biol 11(3):e1001510

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Persi MA, Burnham JC, Duhring JL (1985) Effects of carbon dioxide and pH on adhesion of Candida albicans to vaginal epithelial cells. Infect Immun 50(1):82–90

    CAS  PubMed  PubMed Central  Google Scholar 

  • Peters BM, Palmer GE, Nash AK, Lilly EA, Fidel PL Jr, Noverr MC (2014) Fungal morphogenetic pathways are required for the hallmark inflammatory response during Candida albicans vaginitis. Infect Immun 82(2):532–543

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20(1):133–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phan QT, Myers CL, Fu Y, Sheppard DC, Yeaman MR, Welch WH et al (2007) Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol 5(3):e64

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Polke M, Sprenger M, Scherlach K, Alban-Proano MC, Martin R, Hertweck C et al (2017) A functional link between hyphal maintenance and quorum sensing in Candida albicans. Mol Microbiol 103(4):595–617

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Posas F, Saito H (1998) Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. EMBO J 17(5):1385–1394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Posas F, Wurgler-Murphy SM, Maeda T, Witten EA, Thai TC, Saito H (1996) Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 “two-component” osmosensor. Cell 86(6):865–875

    Article  CAS  PubMed  Google Scholar 

  • Posas F, Chambers JR, Heyman JA, Hoeffler JP, de Nadal E, Arino J (2000) The transcriptional response of yeast to saline stress. J Biol Chem 275(23):17249–17255

    Article  CAS  PubMed  Google Scholar 

  • Ramon AM, Fonzi WA (2003) Diverged binding specificity of Rim101p, the Candida albicans ortholog of PacC. Eukaryot Cell 2(4):718–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramon AM, Porta A, Fonzi WA (1999) Effect of environmental pH on morphological development of Candida albicans is mediated via the PacC-related transcription factor encoded by PRR2. J Bacteriol 181(24):7524–7530

    CAS  PubMed  PubMed Central  Google Scholar 

  • Reinke A, Anderson S, McCaffery JM, Yates J 3rd, Aronova S, Chu S et al (2004) TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae. J Biol Chem 279(15):14752–14762

    Article  CAS  PubMed  Google Scholar 

  • Reiser V, Salah SM, Ammerer G (2000) Polarized localization of yeast Pbs2 depends on osmostress, the membrane protein Sho1 and Cdc42. Nat Cell Biol 2(9):620–627

    Article  CAS  PubMed  Google Scholar 

  • Richter K, Haslbeck M, Buchner J (2010) The heat shock response: life on the verge of death. Mol Cell 40(2):253–266

    Article  CAS  PubMed  Google Scholar 

  • Riggle PJ, Andrutis KA, Chen X, Tzipori SR, Kumamoto CA (1999) Invasive lesions containing filamentous forms produced by a Candida albicans mutant that is defective in filamentous growth in culture. Infect Immun 67(7):3649–3652

    CAS  PubMed  PubMed Central  Google Scholar 

  • Robertson LS, Fink GR (1998) The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc Natl Acad Sci U S A 95(23):13783–13787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rohde JR, Cardenas ME (2004) Nutrient signaling through TOR kinases controls gene expression and cellular differentiation in fungi. Curr Top Microbiol Immunol 279:53–72

    CAS  PubMed  Google Scholar 

  • Rohde JR, Bastidas R, Puria R, Cardenas ME (2008) Nutritional control via Tor signaling in Saccharomyces cerevisiae. Curr Opin Microbiol 11(2):153–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roman E, Nombela C, Pla J (2005) The Sho1 adaptor protein links oxidative stress to morphogenesis and cell wall biosynthesis in the fungal pathogen Candida albicans. Mol Cell Biol 25(23):10611–10627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rooney PJ, Klein BS (2002) Linking fungal morphogenesis with virulence. Cell Microbiol 4(3):127–137

    Article  CAS  PubMed  Google Scholar 

  • Rubin-Bejerano I, Mandel S, Robzyk K, Kassir Y (1996) Induction of meiosis in Saccharomyces cerevisiae depends on conversion of the transcriptional represssor Ume6 to a positive regulator by its regulated association with the transcriptional activator Ime1. Mol Cell Biol 16(5):2518–2526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rupp S, Summers E, Lo HJ, Madhani H, Fink G (1999) MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene. EMBO J 18(5):1257–1269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • San Jose C, Monge RA, Perez-Diaz R, Pla J, Nombela C (1996) The mitogen-activated protein kinase homolog HOG1 gene controls glycerol accumulation in the pathogenic fungus Candida albicans. J Bacteriol 178(19):5850–5852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park H, Myers CL, Sheppard DC, Phan QT, Sanchez AA, J EE et al (2005) Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell Microbiol 7(4):499–510

    Article  CAS  Google Scholar 

  • Sanglard D, Hube B, Monod M, Odds FC, Gow NA (1997) A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence. Infect Immun 65(9):3539–3546

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sato T, Watanabe T, Mikami T, Matsumoto T (2004) Farnesol, a morphogenetic autoregulatory substance in the dimorphic fungus Candida albicans, inhibits hyphae growth through suppression of a mitogen-activated protein kinase cascade. Biol Pharm Bull 27(5):751–752

    Article  CAS  PubMed  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 

  • Saville SP, Lazzell AL, Bryant AP, Fretzen A, Monreal A, Solberg EO et al (2006) Inhibition of filamentation can be used to treat disseminated candidiasis. Antimicrob Agents Chemother 50(10):3312–3316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmelzle T, Hall MN (2000) TOR, a central controller of cell growth. Cell 103(2):253–262

    Article  CAS  PubMed  Google Scholar 

  • Schrick K, Garvik B, Hartwell LH (1997) Mating in Saccharomyces cerevisiae: the role of the pheromone signal transduction pathway in the chemotropic response to pheromone. Genetics 147(1):19–32

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schweizer A, Rupp S, Taylor BN, Rollinghoff M, Schroppel K (2000) The TEA/ATTS transcription factor CaTec1p regulates hyphal development and virulence in Candida albicans. Mol Microbiol 38(3):435–445

    Article  CAS  PubMed  Google Scholar 

  • Sentandreu M, Elorza MV, Sentandreu R, Fonzi WA (1998) Cloning and characterization of PRA1, a gene encoding a novel pH-regulated antigen of Candida albicans. J Bacteriol 180(2):282–289

    CAS  PubMed  PubMed Central  Google Scholar 

  • Setiadi ER, Doedt T, Cottier F, Noffz C, Ernst JF (2006) Transcriptional response of Candida albicans to hypoxia: linkage of oxygen sensing and Efg1p-regulatory networks. J Mol Biol 361(3):399–411

    Article  CAS  PubMed  Google Scholar 

  • Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR et al (2009) Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol 19(8):621–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh P, Chauhan N, Ghosh A, Dixon F, Calderone R (2004) SKN7 of Candida albicans: mutant construction and phenotype analysis. Infect Immun 72(4):2390–2394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith RL, Johnson AD (2000) Turning genes off by Ssn6-Tup1: a conserved system of transcriptional repression in eukaryotes. Trends Biochem Sci 25(7):325–330

    Article  CAS  PubMed  Google Scholar 

  • Song W, Carlson M (1998) Srb/mediator proteins interact functionally and physically with transcriptional repressor Sfl1. EMBO J 17(19):5757–5765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song Y, Cheon SA, Lee KE, Lee SY, Lee BK, Oh DB et al (2008) Role of the RAM network in cell polarity and hyphal morphogenesis in Candida albicans. Mol Biol Cell 19(12):5456–5477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song W, Wang H, Chen J (2011) Candida albicans Sfl2, a temperature-induced transcriptional regulator, is required for virulence in a murine gastrointestinal infection model. FEMS Yeast Res 11(2):209–222

    Article  CAS  PubMed  Google Scholar 

  • Sonneborn A, Bockmuhl DP, Gerads M, Kurpanek K, Sanglard D, Ernst JF (2000) Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans. Mol Microbiol 35(2):386–396

    Article  CAS  PubMed  Google Scholar 

  • Sorger PK, Pelham HR (1987) Purification and characterization of a heat-shock element binding protein from yeast. EMBO J 6(10):3035–3041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spiering MJ, Moran GP, Chauvel M, Maccallum DM, Higgins J, Hokamp K et al (2010) Comparative transcript profiling of Candida albicans and Candida dubliniensis identifies SFL2, a C. albicans gene required for virulence in a reconstituted epithelial infection model. Eukaryot Cell. 9(2):251–65

    Article  PubMed  CAS  Google Scholar 

  • Srikantha T, Tsai L, Daniels K, Enger L, Highley K, Soll DR (1998) The two-component hybrid kinase regulator CaNIK1 of Candida albicans. Microbiology 144(Pt 10):2715–2729

    Article  CAS  PubMed  Google Scholar 

  • Stichternoth C, Fraund A, Setiadi E, Giasson L, Vecchiarelli A, Ernst JF (2011) Sch9 kinase integrates hypoxia and CO2 sensing to suppress hyphal morphogenesis in Candida albicans. Eukaryot Cell 10(4):502–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stoldt VR, Sonneborn A, Leuker CE, Ernst JF (1997) Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J 16(8):1982–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su C, Lu Y, Liu H (2013) Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity. Mol Biol Cell 24(3):385–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    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 

  • Sweet DH, Jang YK, Sancar GB (1997) Role of UME6 in transcriptional regulation of a DNA repair gene in Saccharomyces cerevisiae. Mol Cell Biol 17(11):6223–6235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swoboda RK, Bertram G, Budge S, Gooday GW, Gow NA, Brown AJ (1995) Structure and regulation of the HSP90 gene from the pathogenic fungus Candida albicans. Infect Immun 63(11):4506–4514

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tatebayashi K, Tanaka K, Yang HY, Yamamoto K, Matsushita Y, Tomida T et al (2007) Transmembrane mucins Hkr1 and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway. EMBO J 26(15):3521–3533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tebbji F, Chen Y, Sellam A, Whiteway M (2017) The genomic landscape of the fungus-specific SWI/SNF complex subunit, Snf6, in Candida albicans. mSphere 2(6)

    Google Scholar 

  • Thevelein JM, de Winde JH (1999) Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol 33(5):904–918

    Article  CAS  PubMed  Google Scholar 

  • Toda T, Cameron S, Sass P, Zoller M, Scott JD, McMullen B et al (1987a) Cloning and characterization of BCY1, a locus encoding a regulatory subunit of the cyclic AMP-dependent protein kinase in Saccharomyces cerevisiae. Mol Cell Biol 7(4):1371–1377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toda T, Cameron S, Sass P, Zoller M, Wigler M (1987) Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell. 50(2):277–87

    Article  CAS  PubMed  Google Scholar 

  • Trevijano-Contador N, Rueda C, Zaragoza O (2016) Fungal morphogenetic changes inside the mammalian host. Semin Cell Dev Biol 57:100–109

    Article  PubMed  Google Scholar 

  • Tripathi G, Wiltshire C, Macaskill S, Tournu H, Budge S, Brown AJ (2002) Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans. EMBO J 21(20):5448–5456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tyc KM, Herwald SE, Hogan JA, Pierce JV, Klipp E, Kumamoto CA (2016) The game theory of Candida albicans colonization dynamics reveals host status-responsive gene expression. BMC Syst Biol 10:20

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Veri AO, Miao Z, Shapiro RS, Tebbji F, O’Meara TR, Kim SH et al (2018) Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space. PLoS Genet 14(3):e1007270

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vezina C, Kudelski A, Sehgal SN (1975) Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo) 28(10):721–6

    Article  PubMed  Google Scholar 

  • Vilella F, Herrero E, Torres J, de la Torre-Ruiz MA (2005) Pkc1 and the upstream elements of the cell integrity pathway in Saccharomyces cerevisiae, Rom2 and Mtl1, are required for cellular responses to oxidative stress. J Biol Chem 280(10):9149–9159

    Article  CAS  PubMed  Google Scholar 

  • Vinces MD, Haas C, Kumamoto CA (2006) Expression of the Candida albicans morphogenesis regulator gene CZF1 and its regulation by Efg1p and Czf1p. Eukaryot Cell 5(5):825–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vylkova S, Carman AJ, Danhof HA, Collette JR, Zhou H, Lorenz MC (2011) The fungal pathogen Candida albicans autoinduces hyphal morphogenesis by raising extracellular pH. MBio 2(3):e00055–11

    Google Scholar 

  • Wang Y, Cao YY, Jia XM, Cao YB, Gao PH, Fu XP et al (2006) Cap1p is involved in multiple pathways of oxidative stress response in Candida albicans. Free Radic Biol Med 40(7):1201–1209

    Article  CAS  PubMed  Google Scholar 

  • Weiss EL, Kurischko C, Zhang C, Shokat K, Drubin DG, Luca FC (2002) The Saccharomyces cerevisiae Mob2p-Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell-specific localization of Ace2p transcription factor. J Cell Biol 158(5):885–900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White SJ, Rosenbach A, Lephart P, Nguyen D, Benjamin A, Tzipori S et al (2007) Self-regulation of Candida albicans population size during GI colonization. PLoS Pathog 3(12):e184

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Whiteway M, Bachewich C (2007) Morphogenesis in Candida albicans. Annu Rev Microbiol 61:529–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whiteway M, Dignard D, Thomas DY (1992) Dominant negative selection of heterologous genes: isolation of Candida albicans genes that interfere with Saccharomyces cerevisiae mating factor-induced cell cycle arrest. Proc Natl Acad Sci U S A 89(20):9410–9414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiederrecht G, Shuey DJ, Kibbe WA, Parker CS (1987) The Saccharomyces and Drosophila heat shock transcription factors are identical in size and DNA binding properties. Cell 48(3):507–515

    Article  CAS  PubMed  Google Scholar 

  • Wullschleger S, Loewith R, Oppliger W, Hall MN (2005) Molecular organization of target of rapamycin complex 2. J Biol Chem 280(35):30697–30704

    Article  CAS  PubMed  Google Scholar 

  • Xu XL, Lee RT, Fang HM, Wang YM, Li R, Zou H et al (2008) Bacterial peptidoglycan triggers Candida albicans hyphal growth by directly activating the adenylyl cyclase Cyr1p. Cell Host Microbe 4(1):28–39

    Article  CAS  PubMed  Google Scholar 

  • Xue Y, Batlle M, Hirsch JP (1998) GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p G subunit and functions in a Ras-independent pathway. EMBO J 17(7):1996–2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang W, Yan L, Wu C, Zhao X, Tang J (2014) Fungal invasion of epithelial cells. Microbiol Res 169(11):803–810

    Article  CAS  PubMed  Google Scholar 

  • Zakikhany K, Naglik JR, Schmidt-Westhausen A, Holland G, Schaller M, Hube B (2007) In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination. Cell Microbiol 9(12):2938–2954

    Article  CAS  PubMed  Google Scholar 

  • Zeidler U, Lettner T, Lassnig C, Muller M, Lajko R, Hintner H et al (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

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, De Micheli M, Coleman ST, Sanglard D, Moye-Rowley WS (2000) Analysis of the oxidative stress regulation of the Candida albicans transcription factor, Cap1p. Mol Microbiol 36(3):618–629

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu C, Byers KJ, McCord RP, Shi Z, Berger MF, Newburger DE et al (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Znaidi S, Barker KS, Weber S, Alarco AM, Liu TT, Boucher G et al (2009) Identification of the Candida albicans Cap1p regulon. Eukaryot Cell 8(6):806–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Znaidi S, Nesseir A, Chauvel M, Rossignol T, d’Enfert C (2013) A comprehensive functional portrait of two heat shock factor-type transcriptional regulators involved in Candida albicans morphogenesis and virulence. PLoS Pathog 9(8):e1003519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work has been supported by grants from the Agence Nationale de la Recherche (CANDIHUB, ANR-14-CE-0018), the French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID), the European Commission (FinSysB PITN-GA-2008-214004), and the Wellcome Trust (The Candida albicans ORFeome project, WT088858MA). S.Z. is an Institut Pasteur International Network Affiliate Program Fellow. S.Z. was the recipient of postdoctoral fellowships from the European Commission (FINSysB, PITN-GA-2008-214004), the Agence Nationale de la Recherche (KANJI, ANR-08-MIE-033-01), and the French Government’s Investissement d’Avenir program (Institut de Recherche Technologique BIOASTER, ANR-10-AIRT-03). V.B. was supported by a grant from the Pasteur-Paris University (PPU) International PhD program and the “Fondation Daniel et Nina Carasso.”

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Sadri Znaidi or Sophie Bachellier-Bassi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Basso, V., d’Enfert, C., Znaidi, S., Bachellier-Bassi, S. (2018). From Genes to Networks: The Regulatory Circuitry Controlling Candida albicans Morphogenesis. In: Rodrigues, M. (eds) Fungal Physiology and Immunopathogenesis . Current Topics in Microbiology and Immunology, vol 422. Springer, Cham. https://doi.org/10.1007/82_2018_144

Download citation

Publish with us

Policies and ethics