Chapter 22 : Toward a Molecular Understanding of Virulence

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

Preview this chapter:
Zoom in

Toward a Molecular Understanding of Virulence, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap22-1.gif /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap22-2.gif


It is well known that putative virulence factors include adhesins, the secretion of hydrolytic enzymes, cellular morphogenesis, and phenotypic switching. In this chapter, the authors argue in favor of the recent suggestion that virulence factors are expressed at the cell surface and contribute directly to fungus-host interactions. However, the chapter also highlights the importance of fitness attributes for virulence. The overall aim must be to increase the precision with which the roles of specific virulence and fitness factors can be dissected. If the consequence of virulence is host damage and the aim is to assess the roles of specific molecular virulence factors in inflicting this damage, then experimental models of infection should permit quantification of such damage. The most widely used animal model of hematogenously disseminated infection (candidemia) involves intravenous challenge of mice with an inoculum that is lethal in virulent, wild-type strains. Its scientific advantage is that it offers high reproducibility and is currently by far the most widely used assay of virulence. One possible conclusion from the very large numbers of putative virulence factors discovered by gene disruption approaches is that is highly susceptible to the consequences of many different gene disruptions. Morphological interchange between yeast, pseudohyphal, and hyphal forms is one of the earliest recognized properties of .

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Temporal stages of infection in a mammalian host. Fungal cells (a) adhere to, and become commensal colonizers of, an epithelial surface (b). Given local deterioration in host defense, the fungi can penetrate epithelial layers (c); they may be able to invade as far as the bloodstream (d), leading to dissemination of fungal propagules, which may adhere to and penetrate vascular endothelia and thus gain access to deep tissues.

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Alarco, A. M.,, A. Marcil,, J. Chen,, B. Suter,, D. Thomas, and, M. Whiteway. 2004. Immune-deficient Drosophila melanogaster: a model for the innate immune response to human fungal pathogens. J. Immunol. 172: 56225628.
2. Alonso-Monge, R.,, F. Navarro-Garcia,, G. Molero,, R. Diez-Orejas,, M. Gustin,, J. Pla,, M. Sanchez, and, C. Nombela. 1999. Role of the mitogen-activated protein kinase hog1p in morphogenesis and virulence of Candida albicans. J. Bacteriol. 181: 30583068.
3. Alonso-Monge, R.,, F. Navarro-Garcia,, E. Roman,, A. I. Negredo,, B. Eisman,, U. Nombela, and, J. Pla. 2003. The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans. Eukaryot. Cell 2: 351361.
4. Backen, A. C.,, I. D. Broadbent,, R. W. Fetherston,, J. D. C. Rosamond,, N. F. Schnell, and, M. J. R. Stark. 2000. Evaluation of the CaMAL2 promoter for regulated expression of genes in Candida albicans. Yeast 16: 11211129.
5. Balish, E.,, H. I. Filutowicz, and, T. D. Oberly. 1990. Correlates of cell-mediated immunity in Candida albi-cans-colonized gnotobiotic mice. Infect. Immun. 58: 107113.
6. Barelle, C. J.,, C. L. Manson,, D. M. MacCallum,, F. C. Odds,, N. A. R. Gow, and, A. J. P. Brown. 2004. GFP as a quantitative reporter of gene regulation in Candida albicans. Yeast 21: 333340.
7. Bartie, K. L.,, D. W. Williams,, M. J. Wilson,, A. J. C. Potts, and, M. A. O. Lewis. 2004. Differential invasion of Candida albicans isolates in an in vitro model of oral candidosis. Oral Microbiol. Immunol. 19: 293296.
8. Bendel, C. M.,, K. M. Kinneberg,, R. P. Jechorek,, C. A. Gale,, S. L. Erlandsen,, M. K. Hostetter, and, C. L. Wells. 1999. Systemic infection following intravenous inoculation of mice with Candida albicans int1 mutant strains. Mol. Genet. Metab. 67: 343351.
9. Bennett, R. J., and, A. D. Johnson. 2003. Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains. EMBO J. 22: 25052515.
10. Berman, J., and, P. E. Sudbery. 2002. Candida albicans : a molecular revolution built on lessons from budding yeast. Nat. Rev. Genet. 3: 918930.
11. Bernhardt, J.,, D. Herman,, M. Sheridan, and, R. Calderone. 2001. Adherence and invasion studies of Candida albicans strains, using in vitro models of esophageal candidiasis. J. Infect. Dis. 184: 11701175.
12. Bougnoux, M.-E.,, D. M. Aarensen,, S. Morand,, M. Théraud,, B. G. Spratt, and, C. d’Enfert. 2004. Multilocus sequence typing of Candida albicans: strategies, data exchange and applications. Infect. Genet. Evol. 4: 243252.
13. Bougnoux, M. E.,, A. Tavanti,, C. Bouchier,, N. A. R. Gow,, A. Magnier,, A. D. Davidson,, M. C. J. Maiden,, C. d’Enfert, and, F. C. Odds. 2003. Collaborative consensus for optimized multilocus sequence typing of Candida albicans. J. Clin. Microbiol. 41: 52655266.
14. Brand, A.,, D. M. MacCallum,, A. J. P. Brown,, N. A. R. 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 rein-tegration of URA3 at the RPS10 locus. Mol. Microbiol. 3: 900909.
15. Brennan, M.,, D. Y. Thomas,, M. Whiteway, and, K. Kavanagh. 2002. Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae. FEMS Immunol. Med. Microbiol. 34: 153157.
16. Brown, A. J. P. 2005. Integration of metabolism with virulence in Candida albicans. In A. J. P. Brown (ed.), Fungal Genomics ( Mycota XIII), in press. Springer-Verlag KG, Heidelberg, Germany.
17. Brown, A. J. P. 2002. Morphogenetic signaling pathways in Candida albicans, p. 95106. In R. A. Calderone (ed.), Candida and Candidiasis. ASM Press, Washington, D.C.
18. Bruneau, J. M.,, I. Maillet,, E. Tagat,, R. Legrand,, F. Supatto,, C. Fudali,, J. P. Le Caer,, V. Labas,, D. Lecaque, and, J. Hodgson. 2003. Drug induced proteome changes in Candida albicans : comparison of the effect of beta(1,3) glucan synthase inhibitors and two triazoles, fluconazole and itraconazole. Proteomics 3: 325336.
19. Buurman, E. T.,, C. Westwater,, B. Hube,, A. J. P. Brown,, F. C. Odds, and, N. A. R. Gow. 1998. Molecular analysis of Camnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans. Proc. Nat. Acad. Sci. USA 95: 76707675.
20. Calderone, R. A., and, W. A. Fonzi. 2001. Virulence factors of Candida albicans. Trends Microbiol. 9: 327335.
21. Calderone, R. A., and, N. A. R. Gow. 2002. Host recognition by Candida species, p. 6786. In R. A. Calderone (ed.), Candida and Candidiasis. ASM Press, Washington, D.C.
22. Care, R. S.,, J. Trevethick,, K. M. Binley, and, P. E. Sudbery. 1999. The MET3 promoter: a new tool for Candida albicans molecular genetics. Mol. Microbiol. 34: 792798.
23. Casadevall, A., and, L. A. Pirofski. 2001. Host-pathogen interactions: the attributes of virulence. J. Infect. Dis. 184: 337344.
24. Chauhan, N.,, D. Inglis,, E. Roman,, J. Pla,, D. M. Li,, J. A. Calera, and, R. Calderone. 2003. Candida albicans response regulator gene SSK1 regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress. Eukaryot. Cell 2: 10181024.
25. Cormack, B. P.,, G. Bertram,, M. Egerton,, N. A. R. Gow,, S. Falkow, and, A. J. P. Brown. 1997. Yeast-enhanced green fluorescent protein (yEGFP)—a reporter of gene expression in Candida albicans. Microbiology 143: 303311.
26. Cowen, L. E.,, A. Nantel,, M. S. Whiteway,, D. Y. Thomas,, D. C. Tessier,, L. M. Kohn, and, J. B. Anderson. 2002. Population genomics of drug resistance in Candida albicans. Proc. Nat. Acad. Sci. USA 99: 92849289.
27. Cutler, J. E. 1991. Putative virulence factors of Candida albicans. Annu. Rev. Microbiol. 45: 187218.
28. De Bernardis, F.,, R. Lorenzini, and, A. Cassone. 1999. Rat model of Candida vaginal infection, p. 735740. In O. Zak and M. A. Sande (ed.), Handbook of Animal Models of Infection. Academic Press, Inc., San Diego, Calif.
29. De Bernardis, F.,, F. A. Muhlschlegel,, A. Cassone, and, W. A. Fonzi. 1998. The pH of the host niche controls gene expression in and virulence of Candida albicans. Infect. Immun. 66: 33173325.
30. d’Enfert, C.,, S. Goyard,, S. Rodriguez-Arnaveilhe,, L. Frangeul,, L. Jones,, F. Tekaia,, O. Bader,, L. Castillo,, A. Dominguez,, J. Ernst,, C. Fradin,, C. Gaillardin,, S. Garcia-Sanchez,, P. de Groot,, B. Hube,, F. Klis,, S. Krishnamurthy,, D. Kunze,, M.-C. Lopez,, A. Mavor,, N. Martin,, I. Moszer,, D. Onésime,, J. Perez Martin,, R. Sentandreu, and, A. J. P. Brown. 2004. CandidaDB: a genome database for Candida albicans pathogenomics. Nucleic Acids Res. 33: D353357.
31. Dunphy, G. B.,, U. Oberholzer,, M. Whiteway,, R. J. Zakarian, and, I. Boomer. 2003. Virulence of Candida albicans mutants toward larval Galleria mellonella (Insecta, Lepidoptera, Galleridae). Can. J. Microbiol. 49: 514524.
32. Ener, B., and, L. J. Douglas. 1992. Correlation between cell-surface hydrophobicity of Candida albicans and adhesion to buccal epithelial cells. FEMS Microbiol. Lett. 99: 3742.
33. Enloe, B.,, A. Diamond, and, A. P. Mitchell. 2000. A single-transformation gene function test in diploid Candida albicans. J. Bacteriol. 182: 57305736.
34. Ernst, J. F. 2000. Transcription factors in Candida albi-cans— environmental control of morphogenesis. Microbiology 146: 17631774.
35. Falkow, S. 1988. Molecular Koch’s postulates applied to microbial pathogenicity. Rev. Infect. Dis. 10 (Suppl. 2): S274S276.
36. Fidel, P. L., and, J. D. Sobel. 1999. Murine models of Candida vaginal infections, p. 742748. In O. Zak and, M. A. Sande (ed.), Handbook of Animal Models of Infections. Academic Press, Inc., San Diego, Calif.
37. Fonzi, W., and, M. Irwin. 1993. Isogenic strain construction and gene mapping in Candida albicans. Genetics 134: 717728.
38. Fradin, C., and, B. Hube. 2003. Tissue infection and site-specific gene expression in Candida albicans. Adv. Appl. Microbiol. 53: 271290.
39. 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.
40. Fu, Y.,, A. S. Ibrahim,, D. C. Sheppard,, Y. C. Chen,, S. W. French,, J. E. Cutler,, S. G. Filler, and, J. E. Edwards. 2002. Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1 filamentation pathway. Mol. Microbiol. 44: 6172.
41. Gale, C. A.,, C. M. Bendel,, M. Mcclellan,, M. Hauser,, J. M. Becker,, J. Berman, and, M. K. Hostetter. 1998. Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, Int1. Science 279: 13551358.
42. Garcia-Sanchez, S.,, S. Aubert,, I. Iraqui,, G. Janbon,, J. M. Ghigo, and, C. d’Enfert. 2004. Candida albicans biofilms: a developmental state associated with specific and stable gene expression patterns. Eukaryot. Cell 3: 536545.
43. 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.
44. Gola, S.,, R. Martin,, A. Walther,, A. Dunkler, and, J. Wendland. 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.
45. Gow, N. A. R.,, A. J. P. Brown, and, F. C. Odds. 2002. Fungal morphogenesis and host invasion. Curr. Opin. Microbiol. 5: 366371.
46. Gow, N. A. R.,, Y. Knox,, C. A. Munro, and, W. D. Thompson. 2003. Infection of chick chorioallantoic membrane (CAM) as a model for invasive hyphal growth and pathogenesis of Candida albicans. Med. Mycol. 41: 331338.
47. Green, C. B.,, G. Cheng,, J. Chandra,, P. Mukherjee,, M. A. Ghannoum, and, L. L. Hoyer. 2004. RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms. Microbiology 150: 267275.
48. Hajjeh, R. A.,, A. N. Sofair,, L. H. Harrison,, G. M. Lyon,, B. A. Arthington-Skaggs,, S. A. Mirza,, M. Phelan,, J. Morgan,, W. Lee-Yang,, M. A. Ciblak,, L. E. Benjamin,, L. T. Sanza,, S. Huie,, S. F. Yeo,, M. E. Brandt, and, D. W. Warnock. 2004. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J. Clin. Microbiol. 42: 15191527.
49. Hasenclever, H. F., and, W. O. Mitchell. 1961. Antigenic studies of Candida. III. Comparative pathogenicity of Candida albicans group A, group B and Candida stella-toidea. J. Bacteriol. 82: 578581.
50. Hernandez, R.,, C. Nombela,, R. Diez-Orejas, and, C. Gil. 2004. Two-dimensional reference map of Candida albi-cans hyphal forms. Proteomics 4: 374382.
51. Hostetter, M. K. 2000. RGD-mediated adhesion in fungal pathogens of humans, plants and insects. Curr. Opin. Microbiol. 3: 344348.
52. Hoyer, L. L.,, R. Fundyga,, J. E. Hecht,, J. C. Kapteyn,, F. M. Klis, and, J. Arnold. 2001. Characterization of agglutinin-like sequence genes from non- albicans Candida and phylogenetic analysis of the ALS family. Genetics 157: 15551567.
53. Hube, B., and, J. Naglik. 2001. Candida albicans proteinases: resolving the mystery of a gene family. Microbiology 147: 19972005.
54. Hube, B.,, D. Sanglard,, F. C. Odds,, D. Hess,, M. Monod,, W. Schafer,, A. J. P. Brown, and, N. A. R. Gow. 1997. Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect. Immun. 65: 35293538.
55. Hull, C. M.,, R. M. Raisner, and, A. D. Johnson. 2000. Evidence for mating of the “asexual’’ yeast Candida albicans in a mammalian host. Science 289: 307310.
56. Hwang, C. S.,, Y. U. Baek,, H. S. Yim, and, S. O. Kang. 2003. Protective roles of mitochondrial manganese-containing superoxide dismutase against various stresses in Candida albicans. Yeast 20: 929941.
57. Isenberg, H. D.,, J. Allerhand,, J. I. Berkman, and, D. Goldberg. 1963. Immunological and toxic differences between mouse-virulent and mouse-avirulent Candida albicans. J. Bacteriol. 86: 10101018.
58. Johnson, A. 2003. The biology of mating in Candida albicans. Nat. Rev. Microbiol. 1: 106116.
59. 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. Nat. Acad. Sci. USA 101: 73297334.
60. Kvaal, C.,, S. A. Lachke,, T. Srikantha,, K. Daniels,, J. McCoy, and, D. R. Soll. 1999. Misexpression of the opaque-phase-specific gene PEP1 ( SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection. Infect. Immun. 67: 66526662.
61. Kvaal, C. A.,, T. Srikantha, and, D. R. Soll. 1997. Misexpression of the white-phase-specific gene wh11 in the opaque phase of Candida albicans affects switching and virulence. Infect. Immun. 65: 44684475.
62. Kwon-Chung, K. J.,, D. Lehman,, C. Good, and, P. T. Magee. 1985. Genetic evidence for role of extracellular proteinase in virulence of Candida albicans. Infect. Immun. 49: 571575.
63. Lan, C. Y.,, G. Newport,, L. A. Murillo,, T. Jones,, S. Scherer,, R. W. Davis, and, N. Agabian. 2002. Metabolic specialization associated with phenotypic switching in Candida albicans. Proc. Nat. Acad. Sci. USA 99: 1490714912.
64. Lane, S.,, C. Birse,, S. Zhou,, R. Matson, and, H. P. Liu. 2001. DNA array studies demonstrate convergent regulation of virulence factors by Cph1, Cph2, and Efg1 in Candida albicans. J. Biol. Chem. 276: 4898848996.
65. Leuker, C. E.,, A.-M. Hahn, and, J. F. Ernst. 1992. β-Galactosidase of Kluyveromyces lactis (Lac4p) as reporter of gene expression in Candida albicans and C. tropicalis. Mol. Gen. Genet. 235: 235241.
66. Leuker, C. E.,, A. Sonneborn,, S. Delbruck, and, J. F. Ernst. 1997. Sequence and promoter regulation of the pck1 gene encoding phosphoenolpyruvate carboxykinase of the fungal pathogen Candida albicans. Gene 192: 235240.
67. Li, D. M.,, J. Bernhardt, and, R. Calderone. 2002. Temporal expression of the Candida albicans genes CHK1 and CSSK1, adherence, and morphogenesis in a model of reconstituted human esophageal epithelial candidiasis. Infect. Immun. 70: 15581565.
68. Lo, H. J.,, J. R. Köhler,, D. Di,, D. Loebenberg,, A. Cacciapuoti, and, G. R. Fink. 1997. Nonfilamentous C. albicans mutants are avirulent. Cell 90: 939949.
69. Londono, P.,, X. M. Gao,, F. Bowe,, W. L. Mcpheat,, G. Booth, and, G. Dougan. 1998. Evaluation of the intranasal challenge route in mice as a mucosal model for Candida albicans infection. Microbiology 144: 22912298.
70. Lorenz, M. C.,, J. A. Bender, and, G. R. Fink. 2004. Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot. Cell 3: 10761087.
71. Lorenz, M. C., and, G. R. Fink. 2001. The glyoxylate cycle is required for fungal virulence. Nature 412: 8386.
72. Louria, D. B.,, R. G. Brayton, and, G. Finkel. 1963. Studies on the pathogenesis of experimental Candida albicans infections in mice. Sabouraudia 2: 271283.
73. MacCallum, D. M., and, F. C. Odds. 2005. Temporal events in the intravenous challenge model for experimental Candida albicans infections in female mice. Mycoses 48: 151161.
74. Macdonald, F., and, F. C. Odds. 1983. Virulence for mice of a proteinase-secreting strain of Candida albicans and a proteinase-deficient mutant. J. Gen. Microbiol. 129: 421438.
75. Magee, B. B., and, P. T. Magee. 2000. Induction of mating in Candida albicans by construction of MTL a and MTLα strains. Science 289: 310313.
76. Marcil, A.,, D. Harcus,, D. Y. Thomas, and, M. Whiteway. 2002. Candida albicans killing by RAW 264.7 mouse macrophage cells: effects of Candida genotype, infection ratios, and gamma interferon treatment. Infect. Immun. 70: 63196329.
77. Martchenko, M.,, A. M. Alarco,, D. Harcus, and, M. Whiteway. 2004. Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene. Mol. Biol. Cell 15: 456467.
78. Michel, S.,, S. Ushinsky,, B. Klebl,, E. Leberer,, D. Thomas,, M. Whiteway, and, J. Morschhauser. 2002. Generation of conditional lethal Candida albicans mutants by inducible deletion of essential genes. Mol. Microbiol. 46: 269280.
79. 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.
80. Morschhauser, J.,, S. Michel, and, P. Staib. 1999. Sequential gene disruption in Candida albicans by FLP-mediated site-specific recombination. Mol. Microbiol. 32: 547556.
81. Munro, C. A.,, S. Bates,, E. T. Buurman,, H. B. Hughes,, D. M. MacCallum,, G. Bertram,, A. Atrih,, M. A. J. Ferguson,, J. M. Bain,, A. Brand,, S. Hamilton,, C. Westwater,, L. M. Thomson,, A. J. P. Brown,, F. C. Odds, and, N. A. R. Gow. 2005. Mnt1p and Mnt2p of Candida albicans are partially redundant α-1,2-mannosyltranferases that participate in O-linked mannosylation and are required for adhesion and virulence. J. Biol. Chem. 280: 10511060.
82. Munro, C. A.,, K. Winter,, A. Buchan,, K. Henry,, J. M. Becker,, A. J. P. Brown,, C. E. Bulawa, and, N. A. R. Gow. 2001. Chs1 of Candida albicans is an essential chitin synthase required for synthesis of the septum and for cell integrity. Mol. Microbiol. 39: 14141426.
83. Murad, A. M. A.,, P. R. Lee,, I. D. Broadbent,, C. J. Barelle, and, A. J. P. Brown. 2000. CIp10, an efficient and convenient integrating vector for Candida albicans. Yeast 16: 325327.
84. Murad, A. M. A.,, C. d’Enfert,, C. Gaillardin,, H. Tournu,, F. Tekaia,, D. Talibi,, D. Marechal,, V. Marchais,, J. Cottin, and, A. J. P. Brown. 2001. Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1. Mol. Microbiol. 42: 981993.
85. Murad, A. M. A.,, P. Leng,, M. Straffon,, J. Wishart,, S. Macaskill,, D. MacCallum,, N. Schnell,, D. Talibi,, D. Marechal,, F. Tekaia,, C. d’Enfert,, C. Gaillardin,, F. C. Odds, and, A. J. P. Brown. 2001. NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J. 20: 47424752.
86. Naglik, J.,, A. Albrecht,, O. Bader, and, B. Hube. 2004. Candida albicans proteinases and host/pathogen interactions. Cell. Microbiol. 6: 915926.
87. Naglik, J. R.,, S. J. Challacombe, and, B. Hube. 2003. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol. Mol. Biol. Rev. 67: 400428.
88. Nakagawa, Y.,, T. Kanbe, and, I. Mizuguchi. 2003. Disruption of the human pathogenic yeast Candida albi-cans catalase gene decreases survival in mouse-model infection and elevates susceptibility to higher temperature and to detergents. Microbiol. Immunol. 47: 395403.
89. 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.
90. 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.
91. Navarro-Garcia, F.,, M. Sanchez,, C. Nombela, and, J. Pla. 2001. Virulence genes in the pathogenic yeast Candida albicans. FEMS Microbiol. Rev. 25: 245268.
92. Odds, F. C. 1988. Candida and Candidosis, 2nd ed. Bailliere Tindall, London, United Kingdom.
93. Odds, F. C. 1994. Pathogenesis of Candida infections. J. Am. Acad. Dermatol. 31: S2S5.
94. Odds, F. C. 1997. Switch of phenotype as an escape mechanism of the intruder. Mycoses 40: 912.
95. Odds, F. C.,, R. A. Calderone,, B. Hube, and, C. Nombela. 2003. Virulence in Candida albicans: views and suggestions from a peer-group workshop. ASM News 69: 5455.
96. Odds, F. C.,, L. Van Nuffel, and, N. A. R. Gow. 2000. Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host. Microbiology 146: 18811889.
97. Pitarch, A.,, M. Sanchez,, C. Nombela, and, C. Gil. 2002. Sequential fractionation and two-dimensional gel analysis unravels the complexity of the dimorphic fungus Candida albicans cell wall proteome. Mol. Cell. Proteomics 1: 967982.
98. Poulain, D., and, T. Jouault. 2004. Candida albicans cell wall glycans, host receptors and responses: elements for a decisive crosstalk. Curr. Opin. Microbiol. 7: 342349.
99. Prigneau, O.,, A. Porta, and, B. Maresca. 2004. Candida albicans CTN gene family is induced during macrophage infection: homology, disruption and phenotypic analysis of CTN3 gene. Fungal Genet. Biol. 41: 783793.
100. Prigneau, O.,, A. Porta,, J. A. Poudrier,, S. Colonna-Romano,, T. Noel, and, B. Maresca. 2003. Genes involved in beta-oxidation, energy metabolism and glyoxylate cycle are induced by Candida albicans during macrophage infection. Yeast 20: 723730.
101. 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.
102. Richardson, M. D., and, H. Smith. 1981. Resistance of virulent and attenuated strains of Candida albicans to intracellular killing by human and mouse phagocytes. J. Infect. Dis. 144: 557564.
103. Rieg, G.,, Y. Fu,, A. S. Ibrahim,, X. Zhou,, S. G. Filler, and, J. E. Edwards. 1999. Unanticipated heterogeneity in growth rate and virulence among Candida albicans AAF1 null mutants. Infect. Immun. 67: 31933198.
104. 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 albi-cans and applications to antifungal drug discovery. Mol. Microbiol. 50: 167181.
105. Rogers, T. J., and, E. Balish. 1980. Immunity to Candida albicans. Microbiol. Rev. 44: 660682.
106. Romani, L.,, F. Bistoni, and, P. Puccetti. 2003. Adaptation of Candida albicans to the host environment: the role of morphogenesis in virulence and survival in mammalian hosts. Curr. Opin. Microbiol. 6: 338343.
107. Rubin-Bejerano, I.,, I. Fraser,, P. Grisafi, and, G. R. Fink. 2003. Phagocytosis by neutrophils induces an amino acid deprivation response in Saccharomyces cerevisiae and Candida albicans. Proc. Natl. Acad. Sci. USA 100: 1100711012.
108. Rüchel, R.,, K. Uhlemann, and, B. Böning. 1983. Secretion of acid proteinases by different species of the genus Candida. Zentbl. Bakteriol. Mikrobiol. Hyg. 1 Abt Origi. A 255: 537578.
109. Sanchez, A. A.,, D. A. Johnston,, C. Myers,, J. E. Edwards,, 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.
110. Sandven, P. 2000. Epidemiology of candidemia. Rev. Iberoam. Micol. 17: 7381.
111. Sanglard, D.,, B. Hube,, M. Monod,, F. C. Odds, and, N. A. R. Gow. 1997. A triple deletion of the secreted aspartyl proteinase genes sap4, sap5, and sap6 of Candida albicans causes attenuated virulence. Infect. Immun. 65: 35393546.
112. Santos, M.,, G. Keith, and, M. Tuite. 1993. Non-standard translational events in Candida albicans mediated by an unusual seryl-transfer RNA with a 5’-CAG-3’ anti-codon. EMBO J. 12: 607616.
113. 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.
114. Schaller, M.,, M. Bein,, H. C. Korting,, S. Baur,, G. Hamm,, M. Monod,, S. Beinhauer, and, B. Hube. 2003. The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium. Infect. Immun. 71: 32273234.
115. Schaller, M.,, U. Boeld,, S. Oberbauer,, G. Hamm,, B. Hube, and, H. C. Korting. 2004. Polymorphonuclear leukocytes (PMNs) induce protective Th1-type cytokine epithelial responses in an in vitro model of oral candidosis. Microbiology 150: 28072813.
116. Schaller, M.,, E. Januschke,, C. Schackert,, B. Woerle, and, H. C. Korting. 2001. Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albi-cans during oral and cutaneous candidosis in vivo. J. Med. Microbiol. 50: 743747.
117. Schaller, M.,, H. C. Korting,, W. Schafer,, J. Bastert,, W. C. Chen, and, B. Hube. 1999. Secreted aspartic proteinase (Sap) activity contributes to tissue damage in a model of human oral candidosis. Mol. Microbiol. 34: 169180.
118. Schaller, M.,, R. Mailhammer, and, H. C. Korting. 2002. Cytokine expression induced by Candida albicans in a model of cutaneous candidosis based on reconstituted human epidermis. J. Med. Microbiol. 51: 672676.
119. Smith, D. A.,, S. Nicholls,, B. A. Morgan,, A. J. P. Brown, and, J. Quinn. 2004. A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans. Mol. Biol. Cell 15: 41794190.
120. Soll, D. R. 2002. Candida commensalism and virulence: the evolution of phenotypic plasticity. Acta Trop. 81: 101110.
121. Soll, D. R. 2004. Mating-type locus homozygosis, phenotypic switching and mating: a unique sequence of dependencies in Candida albicans. Bioessays 26: 1020.
122. Soll, D. R., and, C. Pujol. 2003. Candida albicans clades. FEMS Immunol. Med. Microbiol. 39: 17.
123. Srikantha, T.,, A. Klapach,, W. W. Lorenz,, L. K. Tsai,, L. A. Laughlin,, J. A. Gorman, and, D. R. Soll. 1996. The sea pansy Renilla reniformis luciferase serves as a sensitive bioluminescent reporter for differential gene expression in Candida albicans. J. Bacteriol. 178: 121129.
124. 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.
125. Staab, J. F., and, P. Sundstrom. 2003. URA3 as a selectable marker for disruption and virulence assessment of Candida albicans genes. Trends Microbiol. 11: 6973.
126. Staib, F. 1965. Serum-proteins as nitrogen source for yeast-like fungi. Sabouraudia 4: 187193.
127. 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.
128. Tavanti, A.,, A. D. Davidson,, M. J. Fordyce,, N. A. R. Gow,, M. C. J. Maiden, and, F. C. Odds. 2005. Candida albicans : populations and properties determined by multi-locus sequence typing. J. Clin. Microbiol. 44: 56015613.
129. Timpel, C.,, S. Strahlbolsinger,, K. Ziegelbauer, and, J. F. Ernst. 1998. Multiple functions of Pmt1p-mediated protein O-mannosylation in the fungal pathogen Candida albicans. J. Biol. Chem. 273: 2083720846.
130. Trick, W. E.,, S. K. Fridkin,, J. R. Edwards,, R. A. Hajjeh, and, R. P. Gaynes. 2002. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clin. Infect. Dis. 35: 627630.
131. Tsong, A. E.,, M. G. Miller,, R. M. Raisner, and, A. D. Johnson. 2003. Evolution of a combinatorial transcriptional circuit: a case study in yeasts. Cell 115: 389399.
132. Tsuchimori, N.,, L. L. Sharkey,, W. A. Fonzi,, S. W. French,, J. E. Edwards, and, S. G. Filler. 2000. Reduced virulence of HWP1-deficient mutants of Candida albicans and their interactions with host cells. Infect. Immun. 68: 19972002.
133. Tzung, K. W.,, R. M. Williams,, S. Scherer,, N. Federspiel,, T. Jones,, N. Hansen,, V. Bivolarevic,, L. Huizar,, C. Komp,, R. Surzycki,, R. Tamse,, R. W. Davis, and, N. Agabian. 2001. Genomic evidence for a complete sexual cycle in Candida albicans. Proc. Nat. Acad. Sci. USA 98: 32493253.
134. Uhl, M. A., and, A. D. Johnson. 2001. Development of Streptococcus thermophilus lacZ as a reporter gene for Candida albicans. Microbiology 147: 11891195.
135. Wach, A.,, A. Brachat,, R. Pohlmann, and, P. Philippsen. 1994. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10: 17931808.
136. 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.
137. 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.
138. Wisplinghoff, H.,, H. Seifert,, R. P. Wenzel, and, M. B. Edmond. 2003. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin. Infect. Dis. 36: 11031110.
139. Wysong, D. R.,, L. Christin,, A. M. Sugar,, P. W. Robbins, and, R. D. Diamond. 1998. Cloning and sequencing of a Candida albicans catalase gene and effects of disruption of this gene. Infect. Immun. 66: 19531961.
140. Yesland, K., and, W. A. Fonzi. 2000. Allele-specific gene targeting in Candida albicans results from heterology between alleles. Microbiology 146: 20972104.
141. Yin, Z. K.,, D. Stead,, L. Selway,, J. Walker,, I. Riba-Garcia,, T. McInerney,, S. Gaskell,, S. G. Oliver,, P. Cash, and, A. J. P. Brown. 2004. Proteomic response to amino acid starvation in Candida albicans and Saccharomyces cerevisiae. Proteomics 4: 24252436.
142. Zhao, X. J.,, G. E. McElhaney-Feser,, W. H. Bowen,, M. F. Cole,, S. E. Broedel, and, R. L. Cihlar. 1996. Requirement for the Candida albicans fas2 gene for infection in a rat model of oropharyngeal candidiasis. Microbiology 142: 25092514.


Generic image for table
Table 1.

Notes on virulence assays in the murine intravenous-challenge model of disseminated infection

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22
Generic image for table
Table 2.

Notes on the construction of knockout mutants for virulence studies

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22

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