Chapter 46 : The Fungal Pathogen

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

The Fungal Pathogen , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816636/9781555814731_Chap46-1.gif /docserver/preview/fulltext/10.1128/9781555816636/9781555814731_Chap46-2.gif


Research on is driven by the major questions regarding any infectious microbe. This chapter first introduces the medical problem and then animal models of infection and genetic tools for manipulation. It then focuses on three topics-morphogenesis, adherence, and azole drug resistance-that have long held the attention of our research community, in order to give the reader a sense of key questions and prospects for future study. There is a growing selection of minihost models. Models such as , , and cannot recapitulate all of the complexity of mammalian infection, but they lend themselves to highthroughput screens that would be prohibitive for many reasons with mammalian hosts. The glycophosphatidylinositol (GPI) proteins of are linked to the β-1,6 glucans, and for many, their expression can vary depending on morphology. A final thought is that natural selection has probably acted on most strongly as a commensal. Its functional repertoire has likely evolved to avoid inflammation of host tissues and to support effective competition with its bacterial cohabitants. The true logic behind deployment of virulence factors may be most apparent when they are viewed as commensalism factors.

Citation: Fanning S, Mitchell A. 2010. The Fungal Pathogen , p 751-768. In Borkovich K, Ebbole D (ed), Cellular and Molecular Biology of Filamentous Fungi. ASM Press, Washington, DC. doi: 10.1128/9781555816636.ch46

Key Concept Ranking

Restriction Fragment Length Polymorphism
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Alani, E.,, L. Cao, and, N. Kleckner. 1987. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics 116:541545.
2. Alvarez, F. J.,, L. M. Douglas,, A. Rosebrock, and, J. B. Konopka. 2008. The Sur7 protein regulates plasma membrane organization and prevents intracellular cell wall growth in Candida albicans. Mol. Biol. Cell 19:52145225.
3. Alvarez, F. J., and, J. B. Konopka. 2007. Identification of an N-acetylglucosamine transporter that mediates hyphal induction in Candida albicans. Mol. Biol. Cell 18:965975.
4. Andes, D.,, J. Nett,, P. Oschel,, R. Albrecht,, K. Marchillo, and, A. Pitula. 2004. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect. Immun. 72:60236031.
5. Arnaud, M. B.,, M. C. Costanzo,, M. S. Skrzypek,, P. Shah,, G. Binkley,, C. Lane,, S. R. Miyasato, and, G. Sherlock. 2007. Sequence resources at the Candida Genome Database. Nucleic Acids Res. 35:D452D456.
6. Badrane, H.,, S. Cheng,, M. H. Nguyen,, H. Y. Jia,, Z. Zhang,, N. Weisner, and, C. J. Clancy. 2005. Candida albicans IRS4 contributes to hyphal formation and virulence after the initial stages of disseminated candidiasis. Microbiology 151:29232931.
7. Baek, Y. U.,, S. J. Martin, and, D. A. Davis. 2006. Evidence for novel pH-dependent regulation of Candida albicans Rim101, a direct transcriptional repressor of the cell wall beta-glycosidase Phr2. Eukaryot. Cell 5:15501559.
8. Bailey, D. A.,, P. J. Feldmann,, M. Bovey,, N. A. Gow, and, A. J. Brown. 1996. The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins. J. Bacteriol. 178:53535360.
9. Bauer, J., and, J. Wendland. 2007. Candida albicans Sfl1 suppresses flocculation and filamentation. Eukaryot. Cell 6:17361744.
10. Ben-Yaacov, R.,, S. Knoller,, G. A. Caldwell,, J. M. Becker, and, Y. Koltin. 1994. Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene. Antimicrob. Agents Chemother. 38:648652.
11. Berman, J. 2006. Morphogenesis and cell cycle progression in Candida albicans. Curr. Opin. Microbiol. 9:595601.
12. Berman, J., and, P. E. Sudbery. 2002. Candida albicans: a molecular revolution built on lessons from budding yeast. Nat. Rev. Genet. 3:918930.
13. Bignell, E.,, S. Negrete-Urtasun,, A. M. Calcagno,, K. Haynes,, H. N. Arst, Jr., and, T. Rogers. 2005. The Aspergillus pH-responsive transcription factor PacC regulates virulence. Mol. Microbiol. 55:10721084.
14. Biswas, S.,, P. Van Dijck, and, A. Datta. 2007. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol. Mol. Biol. Rev. 71:348376.
15. Blankenship, J. R., and, A. P. Mitchell. 2006. How to build a biofilm: a fungal perspective. Curr. Opin. Microbiol. 9:588594.
16. Brand, A.,, D. M. MacCallum,, A. J. Brown,, N. A. Gow, and, F. C. Odds. 2004. Ectopic expression of URA3 can influence the virulence phenotypes and proteome of Candida albicans but can be overcome by targeted reintegration of URA3 at the RPS10 locus. Eukaryot. Cell 3:900909.
17. Braun, B. R., and, A. D. Johnson. 1997. Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 277:105109.
18. Braun, B. R.,, M. van Het Hoog,, C. d’Enfert,, M. Martchenko,, J. Dungan,, A. Kuo,, D. O. Inglis,, M. A. Uhl,, H. Hogues,, M. Berriman,, M. Lorenz,, A. Levitin,, U. Oberholzer,, C. Bachewich,, D. Harcus,, A. Marcil,, D. Dignard,, T. Iouk,, R. Zito,, L. Frangeul,, F. Tekaia,, K. Rutherford,, E. Wang,, C. A. Munro,, S. Bates,, N. A. Gow,, L. L. Hoyer,, G. Kohler,, J. Morschhauser,, G. Newport,, S. Znaidi,, M. Raymond,, B. Turcotte,, G. Sherlock,, M. Costanzo,, J. Ihmels,, J. Berman,, D. Sanglard,, N. Agabian,, A. P. Mitchell,, A. D. Johnson,, M. Whiteway, and, A. Nantel. 2005. A human-curated annotation of the Candida albicans genome. PLoS Genet. 1:3657.
19. Brown, D. H., Jr.,, A. D. Giusani,, X. Chen, and, C. A. Kumamoto. 1999. Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene. Mol. Microbiol. 34:651662.
20. Bruno, V. M.,, S. Kalachikov,, R. Subaran,, C. J. Nobile,, C. Kyratsous, and, A. P. Mitchell. 2006. Control of the C. albicans cell wall damage response by transcriptional regulator Cas5. PLoS Pathog. 2:e21.
21. Bruno, V. M., and, A. P. Mitchell. 2005. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Mol. Microbiol. 56:559573.
22. Butler, G.,, M. D. Rasmussen,, M. F. Lin,, M. A. Santos,, S. Sakthikumar,, C. A. Munro,, E. Rheinbay,, M. Grabherr,, A. Forche,, J. L. Reedy,, I. Agrafioti,, M. B. Arnaud,, S. Bates,, A. J. Brown,, S. Brunke,, M. C. Costanzo,, D. A. Fitzpatrick,, P. W. de Groot,, D. Harris,, L. L. Hoyer,, B. Hube,, F. M. Klis,, C. Kodira,, N. Lennard,, M. E. Logue,, R. Martin,, A. M. Neiman,, E. Nikolaou,, M. A. Quail,, J. Quinn,, M. C. Santos,, F. F. Schmitzberger,, G. Sherlock,, P. Shah,, K. A. Silverstein,, M. S. Skrzypek,, D. Soll,, R. Staggs,, I. Stansfield,, M. P. Stumpf,, P. E. Sudbery,, T. Srikantha,, Q. Zeng,, J. Berman,, M. Berriman,, J. Heitman,, N. A. Gow,, M. C. Lorenz,, B. W. Birren,, M. Kellis, and, C. A. Cuomo. 2009. Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657662.
23. Casadevall, A., and, L. A. Pirofski. 2003. The damage-response framework of microbial pathogenesis. Nat. Rev. Microbiol. 1:1724.
24. Cegelski, L.,, G. R. Marshall,, G. R. Eldridge, and, S. J. Hultgren. 2008. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6:1727.
25. Chaffin, W. L. 2008. Candida albicans cell wall proteins. Microbiol. Mol. Biol. Rev. 72:495544.
26. Chaffin, W. L.,, J. L. Lopez-Ribot,, M. Casanova,, D. Gozalbo, and, J. P. Martinez. 1998. Cell wall and secreted proteins of Candida albicans: identification, function, and expression. Microbiol. Mol. Biol. Rev. 62:130180.
27. Chamilos, G.,, M. S. Lionakis,, R. E. Lewis,, J. L. Lopez-Ribot,, S. P. Saville,, N. D. Albert,, G. Halder, and, D. P. Kontoyiannis. 2006. Drosophila melanogaster as a facile model for large-scale studies of virulence mechanisms and antifungal drug efficacy in Candida species. J. Infect. Dis. 193:10141022.
28. Chen, C. G.,, Y. L. Yang,, H. I. Shih,, C. L. Su, and, H. J. Lo. 2004. CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1. Antimicrob. Agents Chemother. 48:45054512.
29. Chen, J.,, J. Chen,, S. Lane, and, H. Liu. 2002. A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans. Mol. Microbiol. 46:13351344.
30. Chiang, L. Y.,, D. C. Sheppard,, V. M. Bruno,, A. P. Mitchell,, J. E. Edwards, Jr., and, S. G. Filler. 2007. Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis. Cell. Microbiol. 9:233245.
31. Clemons, K. V.,, G. M. Gonzalez,, G. Singh,, J. Imai,, M. Espiritu,, R. Parmar, and, D. A. Stevens. 2006. Development of an orogastrointestinal mucosal model of candidiasis with dissemination to visceral organs. Antimicrob. Agents Chemother. 50:26502657.
32. Cormack, B. P.,, G. Bertram,, M. Egerton,, N. A. Gow,, S. Falkow, and, A. J. Brown. 1997. Yeast-enhanced green fluorescent protein (yEGFP) a reporter of gene expression in Candida albicans. Microbiology 143(Pt. 2):303311.
33. Coste, A.,, A. Selmecki,, A. Forche,, D. Diogo,, M. E. Bougnoux,, C. d’Enfert,, J. Berman, and, D. Sanglard. 2007. Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot. Cell 6:18891904.
34. Coste, A.,, V. Turner,, F. Ischer,, J. Morschhauser,, A. Forche,, A. Selmecki,, J. Berman,, J. Bille, and, D. Sanglard. 2006. A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics 172:21392156.
35. Coste, A. T.,, M. Karababa,, F. Ischer,, J. Bille, and, D. Sanglard. 2004. TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot. Cell 3:16391652.
36. Cutler, J. E. 1991. Putative virulence factors of Candida albi-cans. Annu. Rev. Microbiol. 45:187218.
37. Davis, D. 2003. Adaptation to environmental pH in Candida albicans and its relation to pathogenesis. Curr. Genet. 44:17.
38. Davis, D. A.,, V. M. Bruno,, L. Loza,, S. G. Filler, and, A. P. Mitchell. 2002. Candida albicans Mds3p, a conserved regulator of pH responses and virulence identified through insertional mutagenesis. Genetics 162:15731581.
39. De Backer, M. D.,, P. T. Magee, and, J. Pla. 2000. Recent developments in molecular genetics of Candida albicans. Annu. Rev. Microbiol. 54:463498.
40. de Repentigny, L.,, D. Lewandowski, and, P. Jolicoeur. 2004. Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin. Microbiol. Rev. 17:729–759, table of contents.
41. Dodgson, A. R.,, K. J. Dodgson,, C. Pujol,, M. A. Pfaller, and, D. R. Soll. 2004. Clade-specific flucytosine resistance is due to a single nucleotide change in the FUR1 gene of Candida albicans. Antimicrob. Agents Chemother. 48:22232227.
42. Donskey, C. J. 2004. The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clin. Infect. Dis. 39:219226.
43. Dujon, B.,, D. Sherman,, G. Fischer,, P. Durrens,, S. Casaregola,, I. Lafontaine,, J. De Montigny,, C. Marck,, C. Neuveglise,, E. Talla,, N. Goffard,, L. Frangeul,, M. Aigle,, V. Anthouard,, A. Babour,, V. Barbe,, S. Barnay,, S. Blanchin,, J. M. Beck-erich,, E. Beyne,, C. Bleykasten,, A. Boisrame,, J. Boyer,, L. Cattolico,, F. Confanioleri,, A. De Daruvar,, L. Despons,, E. Fabre,, C. Fairhead,, H. Ferry-Dumazet,, A. Groppi,, F. Hantraye,, C. Hennequin,, N. Jauniaux,, P. Joyet,, R. Kachouri,, A. Kerrest,, R. Koszul,, M. Lemaire,, I. Lesur,, L. Ma,, H. Muller,, J. M. Nicaud,, M. Nikolski,, S. Oztas,, O. Ozier-Kalogeropoulos,, S. Pellenz,, S. Potier,, G. F. Richard,, M. L. Straub,, A. Suleau,, D. Swennen,, F. Tekaia,, M. Wesolowski-Louvel,, E. Westhof,, B. Wirth,, M. Zeniou-Meyer,, I. Zivanovic,, M. Bolotin-Fukuhara,, A. Thierry,, C. Bouchier,, B. Caudron,, C. Scarpelli,, C. Gaillardin,, J. Weissenbach,, P. Wincker, and, J. L. Souciet. 2004. Genome evolution in yeasts. Nature 430:3544.
44. Enjalbert, B.,, D. M. MacCallum,, F. C. Odds, and, A. J. Brown. 2007. Niche-specific activation of the oxidative stress response by the pathogenic fungus Candida albicans. Infect. Immun. 75:21432151.
45. Enloe, B.,, A. Diamond, and, A. P. Mitchell. 2000. A single-transformation gene function test in diploid Candida albicans. J. Bacteriol. 182:57305736.
46. Falkow, S. 2004. Molecular Koch’s postulates applied to bacterial pathogenicity—a personal recollection 15 years later. Nat. Rev. Microbiol. 2:6772.
47. Fidel, P. L., Jr., and, J. D. Sobel. 1996. Immunopathogenesis of recurrent vulvovaginal candidiasis. Clin. Microbiol. Rev. 9:335348.
48. Finlay, B. B., and, S. Falkow. 1997. Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61:136169.
49. Fonzi, W. A., and, M. Y. Irwin. 1993. Isogenic strain construction and gene mapping in Candida albicans. Genetics 134:717728.
50. Forche, A.,, K. Alby,, D. Schaefer,, A. D. Johnson,, J. Berman, and, R. J. Bennett. 2008. The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains. PLoS Biol. 6:e110.
51. Fradin, C.,, M. Kretschmar,, T. Nichterlein,, C. Gaillardin,, C. d’Enfert, and, B. Hube. 2003. Stage-specific gene expression of Candida albicans in human blood. Mol. Microbiol. 47:15231543.
52. Fu, Y.,, S. G. Filler,, B. J. Spellberg,, W. Fonzi,, A. S. Ibrahim,, T. Kanbe,, M. A. Ghannoum, and, J. E. Edwards, Jr. 1998a. Cloning and characterization of CAD1/AAF1, a gene from Candida albicans that induces adherence to endothelial cells after expression in Saccharomyces cerevisiae. Infect. Immun. 66:20782084.
53. Fu, Y.,, G. Rieg,, W. A. Fonzi,, P. H. Belanger,, J. E. Edwards, Jr., and, S. G. Filler. 1998b. Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces adherence to endothelial and epithelial cells. Infect. Immun. 66:17831786.
54. Fuchs, B. B., and, E. Mylonakis. 2006. Using non-mammalian hosts to study fungal virulence and host defense. Curr. Opin. Microbiol. 9:346351.
55. Gerami-Nejad, M.,, J. Berman, and, C. A. Gale. 2001. Cassettes for PCR-mediated construction of green, yellow, and cyan fluorescent protein fusions in Candida albicans. Yeast 18:859864.
56. Gerami-Nejad, M.,, K. Dulmage, and, J. Berman. 2009. Additional cassettes for epitope and fluorescent fusion proteins in Candida albicans. Yeast 26:399406.
57. Gerami-Nejad, M.,, D. Hausauer,, M. McClellan,, J. Berman, and, C. Gale. 2004. Cassettes for the PCR-mediated construction of regulatable alleles in Candida albicans. Yeast 21:429436.
58. Gimeno, C. J., and, G. R. Fink. 1994. Induction of pseudohyphal growth by overexpression of PHD1, a Saccharomyces cerevisiae gene related to transcriptional regulators of fungal development. Mol. Cell. Biol. 14:21002112.
59. Gola, S.,, R. Martin,, A. Walther,, A. Dunkler, and, J. Wend-land. 2003. New modules for PCR-based gene targeting in Candida albicans: rapid and efficient gene targeting using 100 bp of flanking homology region. Yeast 20:13391347.
60. Gomes, A. C.,, I. Miranda,, R. M. Silva,, G. R. Moura,, B. Thomas,, A. Akoulitchev, and, M. A. Santos. 2007. A genetic code alteration generates a proteome of high diversity in the human pathogen Candida albicans. Genome Biol. 8:R206.
61. Gow, N. A.,, A. J. Brown, and, F. C. Odds. 2002. Fungal morphogenesis and host invasion. Curr. Opin. Microbiol. 5:366371.
62. Gudlaugsson, O.,, S. Gillespie,, K. Lee,, J. Vande Berg,, J. Hu,, S. Messer,, L. Herwaldt,, M. Pfaller, and, D. Diekema. 2003. Attributable mortality of nosocomial candidemia, revisited. Clin. Infect. Dis. 37:11721177.
63. Hoyer, L. L. 2001. The ALS gene family of Candida albicans. Trends Microbiol. 9:176180.
64. Ibrahim, A. S.,, B. J. Spellberg,, V. Avanesian,, Y. Fu, and, J. E. Edwards, Jr. 2006. The anti-Candida vaccine based on the recombinant N-terminal domain of Als1p is broadly active against disseminated candidiasis. Infect. Immun. 74:30393041.
65. Ibrahim, A. S.,, B. J. Spellberg,, V. Avenissian,, Y. Fu,, S. G. Filler, and, J. E. Edwards, Jr. 2005. Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect. Immun. 73:9991005.
66. Jones, T.,, N. A. Federspiel,, H. Chibana,, J. Dungan,, S. Kalman,, B. B. Magee,, G. Newport,, Y. R. Thorstenson,, N. Agabian,, P. T. Magee,, R. W. Davis, and, S. Scherer. 2004. The diploid genome sequence of Candida albicans. Proc. Natl. Acad. Sci. USA 101:73297334.
67. Kadosh, D., and, A. D. Johnson. 2005. Induction of the Candida albicans filamentous growth program by relief of transcriptional repression: a genome-wide analysis. Mol. Biol. Cell 16:29032912.
68. Kandasamy, R.,, G. Vediyappan, and, W. L. Chaffin. 2000. Evidence for the presence of pir-like proteins in Candida albicans. FEMS Microbiol. Lett. 186:239243.
69. Karnani, N.,, N. A. Gaur,, S. Jha,, N. Puri,, S. Krishnamurthy,, S. K. Goswami,, G. Mukhopadhyay, and, R. Prasad. 2004. SRE1 and SRE2 are two specific steroid-responsive modules of Candida drug resistance gene 1 (CDR1) promoter. Yeast 21:219239.
70. Kauffman, C. A. 2006. Fungal infections. Proc. Am. Thorac. Soc. 3:3540.
71. Kaufmann, B. B.,, Q. Yang,, J. T. Mettetal, and, A. van Oudenaarden. 2007. Heritable stochastic switching revealed by single-cell genealogy. PLoS Biol. 5:e239.
72. Kelly, M. T.,, D. M. MacCallum,, S. D. Clancy,, F. C. Odds,, A. J. Brown, and, G. Butler. 2004. The Candida albicans CaACE2 gene affects morphogenesis, adherence and virulence. Mol. Microbiol. 53:969983.
73. Kingsbury, J. M.,, A. L. Goldstein, and, J. H. McCusker. 2006. Role of nitrogen and carbon transport, regulation, and metabolism genes for Saccharomyces cerevisiae survival in vivo. Eukaryot. Cell 5:816824.
74. Klengel, T.,, W. J. Liang,, J. Chaloupka,, C. Ruoff,, K. Schroppel,, J. R. Naglik,, S. E. Eckert,, E. G. Mogensen,, K. Haynes,, M. F. Tuite,, L. R. Levin,, J. Buck, and, F. A. Muhlschlegel. 2005. Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr. Biol. 15:20212026.
75. Kobayashi, S. D., and, J. E. Cutler. 1998. Candida albicans hyphal formation and virulence: is there a clearly defined role? Trends Microbiol. 6:9294.
76. Koh, A. Y.,, J. R. Kohler,, K. T. Coggshall,, N. Van Rooijen, and, G. B. Pier. 2008. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathog. 4:e35.
77. Kurtz, M. B.,, M. W. Cortelyou, and, D. R. Kirsch. 1986. Integrative transformation of Candida albicans, using a cloned Candida ADE2 gene. Mol. Cell. Biol. 6:142149.
78. Kurtz, M. B., and, J. Marrinan. 1989. Isolation of hem3 mutants from Candida albicans by sequential gene disruption. Mol. Gen. Genet. 217:4752.
79. Lavoie, H.,, A. Sellam,, C. Askew,, A. Nantel, and, M. White-way. 2008. A toolbox for epitope-tagging and genome-wide location analysis in Candida albicans. BMC Genomics 9:578.
80. Lay, J.,, L. K. Henry,, J. Clifford,, Y. Koltin,, C. E. Bulawa, and, J. M. Becker. 1998. Altered expression of selectable marker URA3 in gene-disrupted Candida albicans strains complicates interpretation of virulence studies. Infect. Immun. 66:53015306.
81. Leuker, C. E.,, A. M. Hahn, and, J. F. Ernst. 1992. beta-Galactosidase of Kluyveromyces lactis (Lac4p) as reporter of gene expression in Candida albicans and C. tropicalis. Mol. Gen. Genet. 235:235241.
82. Li, F., and, S. P. Palecek. 2008. Distinct domains of the Candida albicans adhesin Eap1p mediate cell-cell and cell-substrate interactions. Microbiology 154:11931203.
83. Li, F., and, S. P. Palecek. 2003. EAP1, a Candida albicans gene involved in binding human epithelial cells. Eukaryot. Cell 2:12661273.
84. Li, F.,, M. J. Svarovsky,, A. J. Karlsson,, J. P. Wagner,, K. Marchillo,, P. Oshel,, D. Andes, and, S. P. Palecek. 2007. Eap1p, an adhesin that mediates Candida albicans biofilm formation in vitro and in vivo. Eukaryot. Cell 6:931939.
85. Liu, H.,, J. Kohler, and, G. R. Fink. 1994. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266:17231726.
86. Lo, H. J.,, J. R. Kohler,, B. DiDomenico,, D. Loebenberg,, A. Cacciapuoti, and, G. R. Fink. 1997. Nonfilamentous C. albicans mutants are avirulent. Cell 90:939949.
87. Lorenz, M. C.,, J. A. Bender, and, G. R. Fink. 2004. Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot. Cell 3:10761087.
88. Magee, B. B.,, M. Legrand,, A. M. Alarco,, M. Raymond, and, P. T. Magee. 2002. Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans. Mol. Microbiol. 46:13451351.
89. Maidan, M. M.,, L. De Rop,, J. Serneels,, S. Exler,, S. Rupp,, H. Tournu,, J. M. Thevelein, and, P. Van Dijck. 2005. The G protein-coupled receptor Gpr1 and the Galpha protein Gpa2 act through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans. Mol. Biol. Cell 16:19711986.
90. Manoharlal, R.,, N. A. Gaur,, S. L. Panwar,, J. Morschhauser, and, R. Prasad. 2008. Transcriptional activation and increased mRNA stability contribute to overexpression of CDR1 in azole-resistant Candida albicans. Antimicrob. Agents Chemother. 52:14811492.
91. Mao, Y.,, Z. Zhang,, C. Gast, and, B. Wong. 2008. C-terminal signals regulate targeting of glycosylphosphatidylinositol-anchored proteins to the cell wall or plasma membrane in Candida albicans. Eukaryot. Cell 7:19061915.
92. Miller, M. G., and, A. D. Johnson. 2002. White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110:293302.
93. Molero, G.,, R. Diez-Orejas,, F. Navarro-Garcia,, L. Monteoliva,, J. Pla,, C. Gil,, M. Sanchez-Perez, and, C. Nombela. 1998. Candida albicans: genetics, dimorphism and pathogenicity. Int. Microbiol. 1:95106.
94. Morschhauser, J.,, K. S. Barker,, T. T. Liu,, B. W. J. Bla,, R. Homayouni, and, P. D. Rogers. 2007. The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog. 3:e164.
95. Morschhauser, J.,, S. Michel, and, J. Hacker. 1998. Expression of a chromosomally integrated, single-copy GFP gene in Candida albicans, and its use as a reporter of gene regulation. Mol. Gen. Genet. 257:412420.
96. Morschhauser, J.,, S. Michel, and, P. Staib. 1999. Sequential gene disruption in Candida albicans by FLP-mediated site-specific recombination. Mol. Microbiol. 32:547556.
97. Morschhauser, J.,, P. Staib, and, G. Kohler. 2005. Targeted gene deletion in Candida albicans wild-type strains by MPAR flipping. Methods Mol. Med. 118:3544.
98. Mylonakis, E., and, A. Aballay. 2005. Worms and flies as genetically tractable animal models to study host-pathogen interactions. Infect. Immun. 73:38333841.
99. Naglik, J.,, A. Albrecht,, O. Bader, and, B. Hube. 2004. Candida albicans proteinases and host/pathogen interactions. Cell. Microbiol. 6:915926.
100. Naglik, J. R.,, S. J. Challacombe, and, B. Hube. 2003. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol. Mol. Biol. Rev. 67:400–428, table of contents.
101. Naglik, J. R.,, G. Newport,, T. C. White,, L. L. Fernandes-Naglik,, J. S. Greenspan,, D. Greenspan,, S. P. Sweet,, S. J. Challacombe, and, N. Agabian. 1999. In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis. Infect. Immun. 67:24822490.
102. Nakayama, H.,, T. Mio,, S. Nagahashi,, M. Kokado,, M. Arisawa, and, Y. Aoki. 2000. Tetracycline-regulatable system to tightly control gene expression in the pathogenic fungus Candida albicans. Infect. Immun. 68:67126719.
103. Nantel, A.,, D. Dignard,, C. Bachewich,, D. Harcus,, A. Marcil,, A. P. Bouin,, C. W. Sensen,, H. Hogues,, M. van het Hoog,, P. Gordon,, T. Rigby,, F. Benoit,, D. C. Tessier,, D. Y. Thomas, and, M. Whiteway. 2002. Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition. Mol. Biol. Cell 13:34523465.
104. Netea, M. G.,, N. A. Gow,, C. A. Munro,, S. Bates,, C. Collins,, G. Ferwerda,, R. P. Hobson,, G. Bertram,, H. B. Hughes,, T. Jansen,, L. Jacobs,, E. T. Buurman,, K. Gijzen,, D. L. Williams,, R. Torensma,, A. McKinnon,, D. M. MacCallum,, F. C. Odds,, J. W. Van der Meer,, A. J. Brown, and, B. J. Kullberg. 2006. Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J. Clin. Investig. 116:16421650.
105. Nobile, C. J.,, D. R. Andes,, J. E. Nett,, F. J. Smith,, F. Yue,, Q. T. Phan,, J. E. Edwards,, S. G. Filler, and, A. P. Mitchell. 2006a. Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog. 2:e63.
106. Nobile, C. J.,, V. M. Bruno,, M. L. Richard,, D. A. Davis, and, A. P. Mitchell. 2003. Genetic control of chlamydospore formation in Candida albicans. Microbiology 149:36293637.
107. Nobile, C. J., and, A. P. Mitchell. 2009. Large-scale gene disruption using the UAU1 cassette. Methods Mol. Biol. 499:175194.
108. Nobile, C. J., and, A. P. Mitchell. 2005. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p. Curr. Biol. 15:11501155.
109. Nobile, C. J.,, J. E. Nett,, D. R. Andes, and, A. P. Mitchell. 2006b. Function of Candida albicans adhesin Hwp1 in biofilm formation. Eukaryot. Cell 5:16041610.
110. Nobile, C. J.,, H. A. Schneider,, J. E. Nett,, D. C. Sheppard,, S. G. Filler,, D. R. Andes, and, A. P. Mitchell. 2008a. Complementary adhesin function in C. albicans biofilm formation. Curr. Biol. 18:10171024.
111. Nobile, C. J.,, N. Solis,, C. L. Myers,, A. J. Fay,, J. S. Deneault,, A. Nantel,, A. P. Mitchell, and, S. G. Filler. 2008b. Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions. Cell. Micro-biol. 10:21802196.
112. Noble, S. M., and, A. D. Johnson. 2007. Genetics of Candida albicans, a diploid human fungal pathogen. Annu. Rev. Genet. 41:193211.
113. Noble, S. M., and, A. D. Johnson. 2005. Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot. Cell 4:298309.
114. Nolte, F. S.,, T. Parkinson,, D. J. Falconer,, S. Dix,, J. Williams,, C. Gilmore,, R. Geller, and, J. R. Wingard. 1997. Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. Antimicrob. Agents Chemother. 41:196199.
115. Noverr, M. C.,, N. R. Falkowski,, R. A. McDonald,, A. N. McKenzie, and, G. B. Huffnagle. 2005. Development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13. Infect. Immun. 73:3038.
116. Park, H.,, C. L. Myers,, D. C. Sheppard,, Q. T. Phan,, A. A. Sanchez,, J. E. Edwards, and, S. G. Filler. 2005. Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell. Microbiol. 7:499510.
117. Park, Y. N., and, J. Morschhauser. 2005. Tetracyclineinducible gene expression and gene deletion in Candida albicans. Eukaryot. Cell 4:13281342.
118. Penalva, M. A., and, H. N. Arst, Jr. 2004. Recent advances in the characterization of ambient pH regulation of gene expression in filamentous fungi and yeasts. Annu. Rev. Micro-biol. 58:425451.
119. Perez, A.,, B. Pedros,, A. Murgui,, M. Casanova,, J. L. Lopez-Ribot, and, J. P. Martinez. 2006. Biofilm formation by Candida albicans mutants for genes coding fungal proteins exhibiting the eight-cysteine-containing CFEM domain. FEMS Yeast Res. 6:10741084.
120. Pfaller, M. A., and, D. J. Diekema. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20:133163.
121. Phan, Q. T.,, C. L. Myers,, Y. Fu,, D. C. Sheppard,, M. R. Yeaman,, W. H. Welch,, A. S. Ibrahim,, J. E. Edwards, Jr., and, S. G. Filler. 2007. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol. 5:e64.
122. Raju, T. N. 1999. The Nobel chronicles. 1958: George Wells Beadle (1903–89), Edward Lawrie Tatum (1909–75) and Joshua Lederberg (b 1925). Lancet 353:2082.
123. Rauceo, J. M.,, N. K. Gaur,, K. G. Lee,, J. E. Edwards,, S. A. Klotz, and, P. N. Lipke. 2004. Global cell surface conformational shift mediated by a Candida albicans adhesin. Infect. Immun. 72:49484955.
124. Reuss, O.,, A. Vik,, R. Kolter, and, J. Morschhauser. 2004. The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341:119127.
125. Richard, M. L.,, C. J. Nobile,, V. M. Bruno, and, A. P. Mitchell. 2005. Candida albicans biofilm-defective mutants. Eukaryot. Cell 4:14931502.
126. Richard, M. L., and, A. Plaine. 2007. Comprehensive analysis of glycosylphosphatidylinositol-anchored proteins in Candida albicans. Eukaryot. Cell 6:119133.
127. Riggle, P. J., and, C. A. Kumamoto. 2006. Transcriptional regulation of MDR1, encoding a drug efflux determinant, in fluconazole-resistant Candida albicans strains through an Mcm1p binding site. Eukaryot. Cell 5:19571968.
128. Roemer, T.,, B. Jiang,, J. Davison,, T. Ketela,, K. Veillette,, A. Breton,, F. Tandia,, A. Linteau,, S. Sillaots,, C. Marta,, N. Martel,, S. Veronneau,, S. Lemieux,, S. Kauffman,, J. Becker,, R. Storms,, C. Boone, and, H. Bussey. 2003. Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol. Microbiol. 50:167181.
129. Rossignol, T.,, P. Lechat,, C. Cuomo,, Q. Zeng,, I. Moszer, and, C. d’Enfert. 2008. CandidaDB: a multi-genome database for Candida species and related Saccharomycotina. Nucleic Acids Res. 36:D557D561.
130. Rubin-Bejerano, I.,, C. Abeijon,, P. Magnelli,, P. Grisafi, and, G. R. Fink. 2007. Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component. Cell Host Microbe 2:5567.
131. Ruiz-Herrera, J.,, M. V. Elorza,, E. Valentin, and, R. Sentandreu. 2006. Molecular organization of the cell wall of Candida albicans and its relation to pathogenicity. FEMS Yeast Res. 6:1429.
132. Samaranayake, Y. H., and, L. P. Samaranayake. 2001. Experimental oral candidiasis in animal models. Clin. Microbiol. Rev. 14:398429.
133. Sanchez, A. A.,, D. A. Johnston,, C. Myers,, J. E. Edwards, Jr.,, A. P. Mitchell, and, S. G. Filler. 2004. Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and endothelial cell damage in vitro. Infect. Immun. 72:598601.
134. Sanglard, D.,, F. Ischer,, M. Monod, and, J. Bille. 1996. Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrob. Agents Chemother. 40:23002305.
135. Saville, S. P.,, A. L. Lazzell,, C. Monteagudo, and, J. L. Lopez-Ribot. 2003. Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot. Cell 2:10531060.
136. Schaller, M.,, H. C. Korting,, C. Borelli,, G. Hamm, and, B. Hube. 2005. Candida albicans-secreted aspartic proteinases modify the epithelial cytokine response in an in vitro model of vaginal candidiasis. Infect. Immun. 73:27582765.
137. Schaller, M.,, W. Schafer,, H. C. Korting, and, B. Hube. 1998. Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity. Mol. Microbiol. 29:605615.
138. Schaub, Y.,, A. Dunkler,, A. Walther, and, J. Wendland. 2006. New pFA-cassettes for PCR-based gene manipulation in Candida albicans. J. Basic Microbiol. 46:416429.
139. Schinabeck, M. K.,, L. A. Long,, M. A. Hossain,, J. Chandra,, P. K. Mukherjee,, S. Mohamed, and, M. A. Ghannoum. 2004. Rabbit model of Candida albicans biofilm infection: liposomal amphotericin B antifungal lock therapy. Antimicrob. Agents Chemother. 48:17271732.
140. Selmecki, A.,, S. Bergmann, and, J. Berman. 2005. Comparative genome hybridization reveals widespread aneuploidy in Candida albicans laboratory strains. Mol. Microbiol. 55:15531565.
141. Selmecki, A.,, A. Forche, and, J. Berman. 2006. Aneuploidy and isochromosome formation in drug-resistant Candida albi-cans. Science 313:367370.
142. Selmecki, A.,, M. Gerami-Nejad,, C. Paulson,, A. Forche, and, J. Berman. 2008. An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. Mol. Microbiol. 68:624641.
143. Sharkey, L. L.,, W. L. Liao,, A. K. Ghosh, and, W. A. Fonzi. 2005. Flanking direct repeats of hisG alter URA3 marker expression at the HWP1 locus of Candida albicans. Microbiology 151:10611071.
144. Shen, J.,, W. Guo, and, J. R. Kohler. 2005. CaNAT1, a heterologous dominant selectable marker for transformation of Candida albicans and other pathogenic Candida species. Infect. Immun. 73:12391242.
145. Sheppard, D. C.,, M. R. Yeaman,, W. H. Welch,, Q. T. Phan,, Y. Fu,, A. S. Ibrahim,, S. G. Filler,, M. Zhang,, A. J. Waring, and, J. E. Edwards, Jr. 2004. Functional and structural diversity in the Als protein family of Candida albicans. J. Biol. Chem. 279:3048030489.
146. Sinha, I.,, Y. M. Wang,, R. Philp,, C. R. Li,, W. H. Yap, and, Y. Wang. 2007. Cyclin-dependent kinases control septin phosphorylation in Candida albicans hyphal development. Dev. Cell 13:421432.
147. Slutsky, B.,, M. Staebell,, J. Anderson,, L. Risen,, M. Pfaller, and, D. R. Soll. 1987. “White-opaque transition”: a second high-frequency switching system in Candida albicans. J. Bacteriol. 169:189197.
148. Sohn, K.,, J. Schwenk,, C. Urban,, J. Lechner,, M. Schweikert, and, S. Rupp. 2006. Getting in touch with Candida albicans: the cell wall of a fungal pathogen. Curr. Drug Targets 7:505512.
149. Sohn, K.,, C. Urban,, H. Brunner, and, S. Rupp. 2003. EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays. Mol. Microbiol. 47:89102.
150. Soll, D. R. 1992. High-frequency switching in Candida albi-cans. Clin. Microbiol. Rev. 5:183203.
151. Soll, D. R. 2004. Mating-type locus homozygosis, phenotypic switching and mating: a unique sequence of dependencies in Candida albicans. Bioessays 26:1020.
152. Spellberg, B. J.,, S. G. Filler, and, J. E. Edwards, Jr. 2006. Current treatment strategies for disseminated candidiasis. Clin. Infect. Dis. 42:244251.
153. Spellberg, B. J.,, A. S. Ibrahim,, V. Avenissian,, S. G. Filler,, C. L. Myers,, Y. Fu, and, J. E. Edwards, Jr. 2005. The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect. Immun. 73:61916193.
154. Staab, J. F.,, S. D. Bradway,, P. L. Fidel, and, P. Sundstrom. 1999. Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283:15351538.
155. Sturtevant, J. 2009. Reporter gene assays in Candida albicans. Methods Mol. Biol. 499:157167.
156. Sudbery, P.,, N. Gow, and, J. Berman. 2004. The distinct morphogenic states of Candida albicans. Trends Microbiol. 12:317324.
157. Sundstrom, P.,, J. E. Cutler, and, J. F. Staab. 2002. Reevaluation of the role of HWP1 in systemic candidiasis by use of Candida albicans strains with selectable marker URA3 targeted to the ENO1 locus. Infect. Immun. 70:32813283.
158. Tielker, D.,, I. Eichhof,, K. E. Jaeger, and, J. F. Ernst. 2009. Flavin mononucleotide-based fluorescent protein as an oxygen-independent reporter in Candida albicans and Saccharomyces cerevisiae. Eukaryot. Cell 8:913915.
159. Tripathi, G.,, C. Wiltshire,, S. Macaskill,, H. Tournu,, S. Budge, and, A. J. Brown. 2002. Gcn4 co-ordinates morpho-genetic and metabolic responses to amino acid starvation in Candida albicans. EMBO J. 21:54485456.
160. Uhl, M. A., and, A. D. Johnson. 2001. Development of Streptococcus thermophilus lacZ as a reporter gene for Candida albicans. Microbiology 147:11891195.
161. Verstrepen, K. J.,, T. B. Reynolds, and, G. R. Fink. 2004. Origins of variation in the fungal cell surface. Nat. Rev. Microbiol. 2:533540.
162. Wellington, M., and, E. Rustchenko. 2005. 5-Fluoro-orotic acid induces chromosome alterations in Candida albicans. Yeast 22:5770.
163. White, S. J.,, A. Rosenbach,, P. Lephart,, D. Nguyen,, A. Benjamin,, S. Tzipori,, M. Whiteway,, J. Mecsas, and, C. A. Kumamoto. 2007. Self-regulation of Candida albicans population size during GI colonization. PLoS Pathog. 3:e184.
164. White, T. C.,, K. A. Marr, and, R. A. Bowden. 1998. Clinical, cellular, and molecular factors that contribute to anti-fungal drug resistance. Clin. Microbiol. Rev. 11:382402.
165. Whiteway, M., and, C. Bachewich. 2007. Morphogenesis in Candida albicans. Annu. Rev. Microbiol. 61:529553.
166. Wilson, R. B.,, D. Davis,, B. M. Enloe, and, A. P. Mitchell. 2000. A recyclable Candida albicans URA3 cassette for PCR product-directed gene disruptions. Yeast 16:6570.
167. Wilson, R. B.,, D. Davis, and, A. P. Mitchell. 1999. Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J. Bacteriol. 181:18681874.
168. Zhang, N.,, A. L. Harrex,, B. R. Holland,, L. E. Fenton,, R. D. Cannon, and, J. Schmid. 2003. Sixty alleles of the ALS7 open reading frame in Candida albicans: ALS7 is a hyper-mutable contingency locus. Genome Res. 13:20052017.
169. Zhao, X.,, S. H. Oh,, G. Cheng,, C. B. Green,, J. A. Nuessen,, K. Yeater,, R. P. Leng,, A. J. Brown, and, L. L. Hoyer. 2004. ALS3 and ALS8 represent a single locus that encodes a Candida albicans adhesin; functional comparisons between Als3p and Als1p. Microbiology 150:24152428.
170. Zordan, R. E.,, M. G. Miller,, D. J. Galgoczy,, B. B. Tuch, and, A. D. Johnson. 2007. Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans. PLoS Biol. 5:e256.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error