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Rôle des gènes RIM et VPS dans la signalisation du pH, la virulence et la résistance aux antifongiques chez la levure Candida albicans.

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Gigou-cornet, Murielle (2006) Rôle des gènes RIM et VPS dans la signalisation du pH, la virulence et la résistance aux antifongiques chez la levure Candida albicans. Doctorat Microbiologie appliquée, Microbiologie, INAPG 2006INAP0037 p.110.

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Résumé

Candida albicans est le premier pathogène fongique de l’homme. Cette levure,

habituellement commensale, peut être à l’origine d’infections profondes mettant en jeu le

pronostic vital. L’incidence des candidoses profondes ne cesse d’augmenter parallèlement à

l’augmentation du nombre de patients à risque. La virulence de C. albicans s’explique par sa

capacité à coloniser puis envahir de nombreux tissus de l’organisme qui constituent autant de

microenvironnements différents. Les réponses adaptatives de la cellule aux modifications

environnementales sont déterminantes pour sa survie et conditionnent sa virulence. La voie

d’endocytose assure la dégradation ou le recyclage des protéines membranaires et joue un rôle

important dans la régulation des récepteurs. Elle est également impliquée dans l’activation de

la voie de signalisation du pH : la voie Rim.

Au début de ce travail, nous avons montré que la voie d’endocytose jouait un rôle

majeur dans la réponse au pH, la morphogenèse et la virulence de C. albicans, de façon à la

fois dépendante et indépendante de la voie Rim. Nous avons montré que les délétions de deux

gènes de la voie d’endocytose, VPS28 et VPS32, produisent non seulement les mêmes effets

que les délétions des gènes de la voie Rim, mais les aggravent.

Nous avons également mis en évidence le rôle de la voie Rim et des protéines Vps

dans la structure de la paroi et la résistance aux antifongiques azolés et aux échinocandines.

Là encore, la voie d’endocytose semble impliquée par son action spécifique dans la voie Rim

mais aussi par d’autres mécanismes indépendants de la voie Rim.

Enfin, nous avons caractérisé les mutants Carim9 et Carim21 et montré que les

protéines Rim9p et Rim21p sont toutes les deux indispensables à l’activation de la voie Rim

chez C. albicans. Ce résultat confirme que le mode d’activation de la voie Rim chez C.

albicans est proche de celui décrit chez S. cerevisiae et diffère sensiblement de celui

d’Aspergillus nidulans ou de Yarrowia lipolytica.

Nous avons montré que l’inhibition de la voie d’endocytose induit chez C. albicans

une réduction majeure de la virulence associée à une augmentation de la sensibilité aux

antifongiques azolés et aux échinocandines. En permettant la potentialisation de l’efficacité

des molécules existantes cette voie pourrait constituer une cible intéressante pour le

développement de nouveaux traitements antifongiques.

Type d'EPrint:Thèse (Doctorat)
Directeur de Mémoire:Gaillardin, Claude
Date:21 Décembre 2006
Jury de Mémoire:Gaillardin, Claude et Bretagne,, Stéphane et Sanglard, Dominique et Dromer,, Françoise et Lavie-Richard, Mathias ,
Ecole Doctorale:ED 435 AGRICULTURE, ALIMENTATION, BIOLOGIE, ENVIRONNEMENTS ET SANTE
Discipline:Microbiologie appliquée
Fonds:INAPG
Institution:INAPG
Laboratoire:Microbiologie
Sujets:7. Sciences de la vie et ingénierie du vivant
Mots-clés libres:Candida albicans, Antifongiques
Code ID:3116
Déposé par :Nadine Pontal
Déposé le :20 Novembre 2007

Références Bibliographiques

Abi-Said, D., E. Anaissie, O. Uzun, I. Raad, H. Pinzcowski, and S. Vartivarian. 1997.

The epidemiology of hematogenous candidiasis caused by different Candida species.

Clin Infect Dis. 24:1122-8.

2. Accoceberry, I., and T. Noel. 2006. [Antifungals cellular targets and mechanisms of

resistance]. Therapie. 61:195-9.

3. Albrecht, A., A. Felk, I. Pichova, J. R. Naglik, M. Schaller, P. de Groot, D. Maccallum,

F. C. Odds, W. Schafer, F. Klis, M. Monod, and B. Hube. 2006. Glycosylphosphatidylinositol-

anchored Proteases of Candida albicans Target Proteins Necessary for

Both Cellular Processes and Host-Pathogen Interactions. J Biol Chem 281:688-694.

4. Arechiga-Carvajal, E. T., and J. Ruiz-Herrera. 2005. The RIM101/pacC homologue

from the basidiomycete Ustilago maydis is functional in multiple pH-sensitive phenomena.

Eukaryot Cell. 4:999-1008.

5. Arst, H. N., and M. A. Penalva. 2003. pH regulation in Aspergillus and parallels with

higher eukaryotic regulatory systems. Trends Genet. 19:224-31.

6. Babst, M. 2005. A protein's final ESCRT. Traffic. 6:2-9.

7. Babst, M., D. J. Katzmann, E. J. Estepa-Sabal, T. Meerloo, and S. D. Emr. 2002. Escrt-

III: an endosome-associated heterooligomeric protein complex required for mvb

sorting. Dev Cell. 3:271-82.

8. Babst, M., B. Wendland, E. J. Estepa, and S. D. Emr. 1998. The Vps4p AAA ATPase

regulates membrane association of a Vps protein complex required for normal endosome

function. Embo J. 17:2982-93.

9. Bachmann, S. P., T. F. Patterson, and J. L. Lopez-Ribot. 2002. In vitro activity of

caspofungin (MK-0991) against Candida albicans clinical isolates displaying different

mechanisms of azole resistance. J Clin Microbiol. 40:2228-30.

10. 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. 5:1550-9.

11. Barwell, K. J., J. H. Boysen, W. Xu, and A. P. Mitchell. 2005. Relationship of DFG16

to the Rim101p pH response pathway in Saccharomyces cerevisiae and Candida albicans.

Eukaryot Cell. 4:890-9.

12. 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 22:2505-15.

88

13. Bennett, R. J., and A. D. Johnson. 2005. Mating in Candida albicans and the search for

a sexual cycle. Annu Rev Microbiol 59:233-55.

14. Bensen, E. S., S. J. Martin, M. Li, J. Berman, and D. A. Davis. 2004. Transcriptional

profiling in Candida albicans reveals new adaptive responses to extracellular pH and

functions for Rim101p. Mol Microbiol. 54:1335-51.

15. Berman, J., and P. E. Sudbery. 2002. Candida Albicans: a molecular revolution built

on lessons from budding yeast. Nat Rev Genet 3:918-30.

16. Bilodeau, P. S., J. L. Urbanowski, S. C. Winistorfer, and R. C. Piper. 2002. The

Vps27p Hse1p complex binds ubiquitin and mediates endosomal protein sorting. Nat

Cell Biol. 4:534-9.

17. Blignaut, E., J. Molepo, C. Pujol, D. R. Soll, and M. A. Pfaller. 2005. Clade-related

amphotericin B resistance among South African Candida albicans isolates. Diagn Microbiol

Infect Dis. 53:29-31.

18. Bow, E. J., M. Laverdiere, N. Lussier, C. Rotstein, M. S. Cheang, and S. Ioannou.

2002. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a

meta analysis of randomized-controlled clinical trials. Cancer. 94:3230-46.

19. Bowers, K., J. Lottridge, S. B. Helliwell, L. M. Goldthwaite, J. P. Luzio, and T. H.

Stevens. 2004. Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces

cerevisiae. Traffic 5:194-210.

20. Bowers, K., S. C. Piper, M. A. Edeling, S. R. Gray, D. J. Owen, P. J. Lehner, and J. P.

Luzio. 2006. Degradation of endocytosed epidermal growth factor and virally ubiquitinated

major histocompatibility complex class I is independent of mammalian ESCRTII.

J Biol Chem. 281:5094-105. Epub 2005 Dec 20.

21. Boysen, J. H., and A. P. Mitchell. 2006. Control of Bro1-domain protein Rim20 localization

by external pH, ESCRT machinery, and the Saccharomyces cerevisiae Rim101

pathway. Mol Biol Cell. 17:1344-53. Epub 2006 Jan 11.

22. 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 34:651-62.

23. Bulawa, C. E., D. W. Miller, L. K. Henry, and J. M. Becker. 1995. Attenuated virulence

of chitin-deficient mutants of Candida albicans. Proc Natl Acad Sci U S A

92:10570-4.

24. Caddick, M. X., A. G. Brownlee, and H. N. Arst, Jr. 1986. Regulation of gene expression

by pH of the growth medium in Aspergillus nidulans. Mol Gen Genet. 203:346-

53.

25. Calabrese, D., J. Bille, and D. Sanglard. 2000. A novel multidrug efflux transporter

gene of the major facilitator superfamily from Candida albicans (FLU1) conferring

resistance to fluconazole. Microbiology. 146:2743-54.

89

26. Calderone, R. G. N. 2002. Host recognition by Candida sp. ASM Press, Washington

DC.

27. Cameron, M. L., W. A. Schell, S. Bruch, J. A. Bartlett, H. A. Waskin, and J. R. Perfect.

1993. Correlation of in vitro fluconazole resistance of Candida isolates in relation

to therapy and symptoms of individuals seropositive for human immunodeficiency virus

type 1. Antimicrob Agents Chemother. 37:2449-53.

28. Caracuel, Z., C. Casanova, M. I. Roncero, A. Di Pietro, and J. Ramos. 2003. pH response

transcription factor PacC controls salt stress tolerance and expression of the PType

Na+ -ATPase Ena1 in Fusarium oxysporum. Eukaryot Cell. 2:1246-52.

29. Castrejon, F., A. Gomez, M. Sanz, A. Duran, and C. Roncero. 2006. The RIM101

pathway contributes to yeast cell wall assembly and its function becomes essential in

the absence of mitogen-activated protein kinase Slt2p. Eukaryot Cell. 5:507-17.

30. Chabasse, D., J. Bouchara, L. De Gentile, and J. Chennebault. 1988. Chlamydospores

de Candida albicans observées in vivo chez un patient atteint de SIDA. . Ann. Biol.

Clin. 46:817-818.

31. Chauhan, N. D. S. P., Calderone R, Kruppa M. 2002. The cell wall of Candida spp.

ASM Press, Washington DC.

32. Chen C, Y. Y., Shih H, Lo H. 2006. REP1 as a negative regulator on fluconazole resistance

in Candida albicans., 46th Interescience Conference of Antimicrobial Agents

and Chemotherapy. , San Francisco, CA. .

33. Chen, J., S. Zhou, Q. Wang, X. Chen, T. Pan, and H. Liu. 2000. Crk1, a novel Cdc2-

related protein kinase, is required for hyphal development and virulence in Candida albicans.

Mol Cell Biol. 20:8696-708.

34. Chen-Wu, J. L., J. Zwicker, A. R. Bowen, and P. W. Robbins. 1992. Expression of

chitin synthase genes during yeast and hyphal growth phases of Candida albicans. Mol

Microbiol 6:497-502.

35. Chiu, Y. S., S. C. Chang, P. R. Hsueh, J. L. Wang, H. Y. Sun, and Y. C. Chen. 2006.

Survey of amphotericin B susceptibility of Candida clinical isolates determined by

Etest. J Microbiol Immunol Infect. 39:335-41.

36. Clemons, K. V., M. Espiritu, R. Parmar, and D. A. Stevens. 2006. Assessment of the

paradoxical effect of caspofungin in therapy of candidiasis. Antimicrob Agents

Chemother. 50:1293-7.

37. CLSI, C. L. S. I. 1997. Reference method for broth dilution antifungal susceptibility

testing of yeasts; approved standard. M27A, . Wayne, PA 1997.15. .

38. 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. 172:2139-56. Epub 2006 Feb 1.

90

39. 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. 3:1639-52.

40. Cowen, L. E., J. B. Anderson, and L. M. Kohn. 2002. Evolution of drug resistance in

Candida albicans. Annu Rev Microbiol. 56:139-65. Epub 2002 Jan 30.

41. Cowen, L. E., and S. Lindquist. 2005. Hsp90 potentiates the rapid evolution of new

traits: drug resistance in diverse fungi. Science. 309:2185-9.

42. Dannaoui, E. a. t. F. M. S. G. 2004. Initiation of an active surveillance program on

yeast-related bloodstream infections in France (ASPYRIF), 14th European Congress

of Clinical Microbiology and Infectious Diseases (ECCMID), 1-4 May 2004, Prague.

Abstract P-986. , Prague.

43. Davis, D. 2003. Adaptation to environmental pH in Candida albicans and its relation

to pathogenesis. Curr Genet. 44:1-7. Epub 2003 Jun 18.

44. Davis, D., R. B. Wilson, and A. P. Mitchell. 2000a. RIM101-dependent and-independent

pathways govern pH responses in Candida albicans. Mol Cell Biol. 20:971-8.

45. Davis, D., J. E. Edwards, Jr., A. P. Mitchell, and A. S. Ibrahim. 2000b. Candida albicans

RIM101 pH response pathway is required for host-pathogen interactions. Infect

Immun. 68:5953-9.

46. 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. 162:1573-81.

47. 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. 66:3317-25.

48. de Groot, P. W., K. J. Hellingwerf, and F. M. Klis. 2003. Genome-wide identification

of fungal GPI proteins. Yeast 20:781-96.

49. Denison, S. H., S. Negrete-Urtasun, J. M. Mingot, J. Tilburn, W. A. Mayer, A. Goel,

E. A. Espeso, M. A. Penalva, and H. N. Arst, Jr. 1998. Putative membrane components

of signal transduction pathways for ambient pH regulation in Aspergillus and

meiosis in saccharomyces are homologous. Mol Microbiol. 30:259-64.

50. Denison, S. H., S. Negrete-Urtasun, J. M. Mingot, J. Tilburn, W. A. Mayer, A. Goel,

E. A. Espeso, M. A. Penalva, and H. N. Arst. 2001. Putative membrane components of

signal transduction pathways for ambient pH regulation in Aspergillus and meiosis in

Saccharomyces are homologous Addendum. Mol Microbiol. 39:211.

91

51. Diez-Orejas, R., G. Molero, F. Navarro-Garcia, J. Pla, C. Nombela, and M. Sanchez-

Perez. 1997. Reduced virulence of Candida albicans MKC1 mutants: a role for mitogen-

activated protein kinase in pathogenesis. Infect Immun. 65:833-7.

52. Douglas, C. M., J. A. D'Ippolito, G. J. Shei, M. Meinz, J. Onishi, J. A. Marrinan, W.

Li, G. K. Abruzzo, A. Flattery, K. Bartizal, A. Mitchell, and M. B. Kurtz. 1997. Identification

of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-Dglucan

synthase inhibitors. Antimicrob Agents Chemother. 41:2471-9.

53. Douglas, C. M., F. Foor, J. A. Marrinan, N. Morin, J. B. Nielsen, A. M. Dahl, P.

Mazur, W. Baginsky, W. Li, M. el-Sherbeini, and et al. 1994. The Saccharomyces

cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit

of 1,3-beta-D-glucan synthase. Proc Natl Acad Sci U S A. 91:12907-11.

54. 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. Beckerich, 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. 430:35-44.

55. Edmond, M. B., S. E. Wallace, D. K. McClish, M. A. Pfaller, R. N. Jones, and R. P.

Wenzel. 1999. Nosocomial bloodstream infections in United States hospitals: a threeyear

analysis. Clin Infect Dis. 29:239-44. Write to the Help Desk NCBI | NLM | NIH

Department of Health & Human Services Privacy Statement | Freedom of Information

Act | Disclaimer Oct 2 2006 08:20:36.

56. Eggimann, P., J. Garbino, and D. Pittet. 2003. Epidemiology of Candida species infections

in critically ill non-immunosuppressed patients. Lancet Infect Dis. 3:685-702.

57. Eisenhaber, B., G. Schneider, M. Wildpaner, and F. Eisenhaber. 2004. A sensitive predictor

for potential GPI lipid modification sites in fungal protein sequences and its application

to genome-wide studies for Aspergillus nidulans, Candida albicans,

Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. J

Mol Biol 337:243-53.

58. Fidel, P. L., Jr., and J. D. Sobel. 1994. The role of cell-mediated immunity in candidiasis.

Trends Microbiol. 2:202-6.

59. Fonzi, W. A. 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

181:7070-9.

92

60. Galagan, J. E., M. R. Henn, L. J. Ma, C. A. Cuomo, and B. Birren. 2005. Genomics of

the fungal kingdom: insights into eukaryotic biology. Genome Res. 15:1620-31.

61. Garcia, R., C. Bermejo, C. Grau, R. Perez, J. M. Rodriguez-Pena, J. Francois, C.

Nombela, and J. Arroyo. 2004. The global transcriptional response to transient cell

wall damage in Saccharomyces cerevisiae and its regulation by the cell integrity signaling

pathway. J Biol Chem. 279:15183-95. Epub 2004 Jan 21.

62. Garrus, J. E., U. K. von Schwedler, O. W. Pornillos, S. G. Morham, K. H. Zavitz, H.

E. Wang, D. A. Wettstein, K. M. Stray, M. Cote, R. L. Rich, D. G. Myszka, and W. I.

Sundquist. 2001. Tsg101 and the vacuolar protein sorting pathway are essential for

HIV-1 budding. Cell. 107:55-65.

63. Garrus, J. E., U. K. von Schwedler, O. W. Pornillos, S. G. Morham, K. H. Zavitz, H.

E. Wang, D. A. Wettstein, K. M. Stray, M. Cote, R. L. Rich, D. G. Myszka, and W. I.

Sundquist. 2001. Tsg101 and the vacuolar protein sorting pathway are essential for

HIV-1 budding. Cell. 107:55-65.

64. Gaur, N. A., R. Manoharlal, P. Saini, T. Prasad, G. Mukhopadhyay, M. Hoefer, J.

Morschhauser, and R. Prasad. 2005. Expression of the CDR1 efflux pump in clinical

Candida albicans isolates is controlled by a negative regulatory element. Biochem

Biophys Res Commun. 332:206-14.

65. Ghannoum, M. A. 2000. Potential role of phospholipases in virulence and fungal

pathogenesis. Clin Microbiol Rev. 13:122-43, table of contents.

66. Ghannoum, M. A., J. H. Rex, and J. N. Galgiani. 1996. Susceptibility testing of fungi:

current status of correlation of in vitro data with clinical outcome. J Clin Microbiol.

34:489-95.

67. Ghannoum, M. A., B. Spellberg, S. M. Saporito-Irwin, and W. A. Fonzi. 1995. Reduced

virulence of Candida albicans PHR1 mutants. Infect Immun. 63:4528-30. Write

to the Help Desk NCBI | NLM | NIH Department of Health & Human Services Privacy

Statement | Freedom of Information Act | Disclaimer Sep 18 2006 12:27:35.

68. Ghannoum, M. A., I. Swairjo, and D. R. Soll. 1990. Variation in lipid and sterol contents

in Candida albicans white and opaque phenotypes. J Med Vet Mycol. 28:103-15.

Write to the Help Desk NCBI | NLM | NIH Department of Health & Human Services

Privacy Statement | Freedom of Information Act | Disclaimer Oct 30 2006 07:27:22.

69. Giusani, A. D., M. Vinces, and C. A. Kumamoto. 2002. Invasive filamentous growth

of Candida albicans is promoted by Czf1p-dependent relief of Efg1p-mediated repression.

Genetics 160:1749-53.

70. Gonzalez-Lopez, C. I., R. Szabo, S. Blanchin-Roland, and C. Gaillardin. 2002. Genetic

control of extracellular protease synthesis in the yeast Yarrowia lipolytica. Genetics.

160:417-27.

71. Gow, N. A., A. J. Brown, and F. C. Odds. 2002. Fungal morphogenesis and host invasion.

Curr Opin Microbiol. 5:366-71.

93

72. Gow, N. A., P. W. Robbins, J. W. Lester, A. J. Brown, W. A. Fonzi, T. Chapman, and

O. S. Kinsman. 1994. A hyphal-specific chitin synthase gene (CHS2) is not essential

for growth, dimorphism, or virulence of Candida albicans. Proc Natl Acad Sci U S A

91:6216-20.

73. 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. 42:1519-27.

74. Han, Y., and J. E. Cutler. 1995. Antibody response that protects against disseminated

candidiasis. Infect Immun 63:2714-9.

75. Hayashi, M., T. Fukuzawa, H. Sorimachi, and T. Maeda. 2005. Constitutive activation

of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the

MVB/ESCRT pathway. Mol Cell Biol. 25:9478-90.

76. Haynes, M. P., P. L. Chong, H. R. Buckley, and R. A. Pieringer. 1996. Fluorescence

studies on the molecular action of amphotericin B on susceptible and resistant fungal

cells. Biochemistry. 35:7983-92.

77. Herranz, S., J. M. Rodriguez, H. J. Bussink, J. C. Sanchez-Ferrero, H. N. Arst, Jr., M.

A. Penalva, and O. Vincent. 2005. Arrestin-related proteins mediate pH signaling in

fungi. Proc Natl Acad Sci U S A. 102:12141-6. Epub 2005 Aug 11.

78. Herrero, A. B., P. Magnelli, M. K. Mansour, S. M. Levitz, H. Bussey, and C. Abeijon.

2004. KRE5 gene null mutant strains of Candida albicans are avirulent and have

altered cell wall composition and hypha formation properties. Eukaryot Cell 3:1423-

32.

79. Hicke, L. 2001. Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol. 2:195-

201.

80. Holz, R. W. 1974. The effects of the polyene antibiotics nystatin and amphotericin B

on thin lipid membranes. Ann N Y Acad Sci. 235:469-79.

81. Hope, W. W., L. Tabernero, D. W. Denning, and M. J. Anderson. 2004. Molecular

mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrob

Agents Chemother. 48:4377-86.

82. Hoyer, L. L., J. Clevenger, J. E. Hecht, E. J. Ehrhart, and F. M. Poulet. 1999. Detection

of Als proteins on the cell wall of Candida albicans in murine tissues. Infect Immun

67:4251-5.

83. Hube. 2002. Extracellular hydrolases. ASM Press, Washington DC.

94

84. Hube, B., F. Stehr, M. Bossenz, A. Mazur, M. Kretschmar, and W. Schafer. 2000.

Secreted lipases of Candida albicans: cloning, characterisation and expression analysis

of a new gene family with at least ten members. Arch Microbiol. 174:362-74.

85. 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 289:307-10.

86. Ito, T., T. Chiba, R. Ozawa, M. Yoshida, M. Hattori, and Y. Sakaki. 2001. A comprehensive

two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad

Sci U S A 98:4569-74.

87. James, T. Y., F. Kauff, C. L. Schoch, P. B. Matheny, V. Hofstetter, C. J. Cox, G.

Celio, C. Gueidan, E. Fraker, J. Miadlikowska, H. T. Lumbsch, A. Rauhut, V. Reeb,

A. E. Arnold, A. Amtoft, J. E. Stajich, K. Hosaka, G. H. Sung, D. Johnson, B.

O'Rourke, M. Crockett, M. Binder, J. M. Curtis, J. C. Slot, Z. Wang, A. W. Wilson, A.

Schussler, J. E. Longcore, K. O'Donnell, S. Mozley-Standridge, D. Porter, P. M.

Letcher, M. J. Powell, J. W. Taylor, M. M. White, G. W. Griffith, D. R. Davies, R. A.

Humber, J. B. Morton, J. Sugiyama, A. Y. Rossman, J. D. Rogers, D. H. Pfister, D.

Hewitt, K. Hansen, S. Hambleton, R. A. Shoemaker, J. Kohlmeyer, B. Volkmann-

Kohlmeyer, R. A. Spotts, M. Serdani, P. W. Crous, K. W. Hughes, K. Matsuura, E.

Langer, G. Langer, W. A. Untereiner, R. Lucking, B. Budel, D. M. Geiser, A. Aptroot,

P. Diederich, I. Schmitt, M. Schultz, R. Yahr, D. S. Hibbett, F. Lutzoni, D. J.

McLaughlin, J. W. Spatafora, and R. Vilgalys. 2006. Reconstructing the early evolution

of Fungi using a six-gene phylogeny. Nature. 443:818-22.

88. 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 U S A

101:7329-34.

89. Jouault, T., C. Fradin, P. A. Trinel, A. Bernigaud, and D. Poulain. 1998. Early signal

transduction induced by Candida albicans in macrophages through shedding of a

glycolipid. J Infect Dis 178:792-802.

90. Kamura, T., D. Burian, H. Khalili, S. L. Schmidt, S. Sato, W. J. Liu, M. N. Conrad, R.

C. Conaway, J. W. Conaway, and A. Shilatifard. 2001. Cloning and characterization

of ELL-associated proteins EAP45 and EAP20. a role for yeast EAP-like proteins in

regulation of gene expression by glucose. J Biol Chem. 276:16528-33. Epub 2001 Feb

5.

91. Kapteyn, J. C., L. L. Hoyer, J. E. Hecht, W. H. Muller, A. Andel, A. J. Verkleij, M.

Makarow, H. Van Den Ende, and F. M. Klis. 2000. The cell wall architecture of Candida

albicans wild-type cells and cell wall-defective mutants. Mol Microbiol 35:601-

11.

92. Karababa, M., E. Valentino, G. Pardini, A. T. Coste, J. Bille, and D. Sanglard. 2006.

CRZ1, a target of the calcineurin pathway in Candida albicans. Mol Microbiol.

59:1429-51.

95

93. Katiyar, S., M. Pfaller, and T. Edlind. 2006. Candida albicans and Candida glabrata

clinical isolates exhibiting reduced echinocandin susceptibility. Antimicrob Agents

Chemother. 50:2892-4.

94. Katoh, K., H. Shibata, H. Suzuki, A. Nara, K. Ishidoh, E. Kominami, T. Yoshimori,

and M. Maki. 2003. The ALG-2-interacting protein Alix associates with CHMP4b, a

human homologue of yeast Snf7 that is involved in multivesicular body sorting. J Biol

Chem. 278:39104-13. Epub 2003 Jul 14.

95. Katzmann, D. J., M. Babst, and S. D. Emr. 2001. Ubiquitin-dependent sorting into the

multivesicular body pathway requires the function of a conserved endosomal protein

sorting complex, ESCRT-I. Cell. 106:145-55.

96. Katzmann, D. J., G. Odorizzi, and S. D. Emr. 2002. Receptor downregulation and

multivesicular-body sorting. Nat Rev Mol Cell Biol. 3:893-905.

97. Ketela, T., R. Green, and H. Bussey. 1999. Saccharomyces cerevisiae mid2p is a potential

cell wall stress sensor and upstream activator of the PKC1-MPK1 cell integrity

pathway. J Bacteriol. 181:3330-40.

98. Kim, M. K., H. S. Park, C. H. Kim, H. M. Park, and W. Choi. 2002. Inhibitory effect

of nikkomycin Z on chitin synthases in Candida albicans. Yeast. 19:341-9.

99. Klionsky, D. J., H. Nelson, and N. Nelson. 1992. Compartment acidification is required

for efficient sorting of proteins to the vacuole in Saccharomyces cerevisiae. J

Biol Chem. 267:3416-22.

100. Kondoh, O., Y. Tachibana, Y. Ohya, M. Arisawa, and T. Watanabe. 1997. Cloning of

the RHO1 gene from Candida albicans and its regulation of beta-1,3-glucan synthesis.

J Bacteriol 179:7734-41.

101. Kullas, A. L., M. Li, and D. A. Davis. 2004. Snf7p, a component of the ESCRT-III

protein complex, is an upstream member of the RIM101 pathway in Candida albicans.

Eukaryot Cell. 3:1609-18.

102. Kullberg, B. J., J. D. Sobel, M. Ruhnke, P. G. Pappas, C. Viscoli, J. H. Rex, J. D.

Cleary, E. Rubinstein, L. W. Church, J. M. Brown, H. T. Schlamm, I. T. Oborska, F.

Hilton, and M. R. Hodges. 2005. Voriconazole versus a regimen of amphotericin B

followed by fluconazole for candidaemia in non-neutropenic patients: a randomised

non-inferiority trial. Lancet. 366:1435-42.

103. Kumamoto, C. A., and M. D. Vinces. 2005. Alternative Candida albicans lifestyles:

growth on surfaces. Annu Rev Microbiol 59:113-33.

104. Lamb, T. M., and A. P. Mitchell. 2003. The transcription factor Rim101p governs ion

tolerance and cell differentiation by direct repression of the regulatory genes NRG1

and SMP1 in Saccharomyces cerevisiae. Mol Cell Biol. 23:677-86.

96

105. Lamb, T. M., W. Xu, A. Diamond, and A. P. Mitchell. 2001. Alkaline response genes

of Saccharomyces cerevisiae and their relationship to the RIM101 pathway. J Biol

Chem 276:1850-6.

106. Lambert, M., S. Blanchin-Roland, F. Le Louedec, A. Lepingle, and C. Gaillardin.

1997. Genetic analysis of regulatory mutants affecting synthesis of extracellular proteinases

in the yeast Yarrowia lipolytica: identification of a RIM101/pacC homolog.

Mol Cell Biol 17:3966-76.

107. Laverdiere, M., R. G. Lalonde, J. G. Baril, D. C. Sheppard, S. Park, and D. S. Perlin.

2006. Progressive loss of echinocandin activity following prolonged use for treatment

of Candida albicans oesophagitis. J Antimicrob Chemother. 57:705-8. Epub 2006 Feb

7.

108. Law, D., C. B. Moore, and D. W. Denning. 1997. Amphotericin B resistance testing of

Candida spp.: a comparison of methods. J Antimicrob Chemother. 40:109-12.

109. Law, D., C. B. Moore, H. M. Wardle, L. A. Ganguli, M. G. Keaney, and D. W. Denning.

1994. High prevalence of antifungal resistance in Candida spp. from patients

with AIDS. J Antimicrob Chemother. 34:659-68.

110. Leberer, E., D. Harcus, D. Dignard, L. Johnson, S. Ushinsky, D. Y. Thomas, and K.

Schroppel. 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. 42:673-87.

111. Leidich, S. D., A. S. Ibrahim, Y. Fu, A. Koul, C. Jessup, J. Vitullo, W. Fonzi, F. Mirbod,

S. Nakashima, Y. Nozawa, and M. A. Ghannoum. 1998. Cloning and disruption

of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans.

J Biol Chem. 273:26078-86.

112. Levin, D. E. 2005. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol

Mol Biol Rev. 69:262-91.

113. Li, M., S. J. Martin, V. M. Bruno, A. P. Mitchell, and D. A. Davis. 2004. Candida albicans

Rim13p, a protease required for Rim101p processing at acidic and alkaline

pHs. Eukaryot Cell. 3:741-51.

114. Lo, H. J., J. R. Kohler, B. DiDomenico, D. Loebenberg, A. Cacciapuoti, and G. R.

Fink. 1997. Nonfilamentous C. albicans mutants are avirulent. Cell. 90:939-49.

115. Lortholary, O. D., F; Dannaoui E;. 2002. Associations d'antifongiques, .

116. Lotz, H., K. Sohn, H. Brunner, F. A. Muhlschlegel, and S. Rupp. 2004. RBR1, a novel

pH-regulated cell wall gene of Candida albicans, is repressed by RIM101 and activated

by NRG1. Eukaryot Cell. 3:776-84.

117. Luhtala, N., and G. Odorizzi. 2004. Bro1 coordinates deubiquitination in the multivesicular

body pathway by recruiting Doa4 to endosomes. J Cell Biol. 166:717-29.

Epub 2004 Aug 23.

97

118. Lussier, M., A. M. White, J. Sheraton, T. di Paolo, J. Treadwell, S. B. Southard, C. I.

Horenstein, J. Chen-Weiner, A. F. Ram, J. C. Kapteyn, T. W. Roemer, D. H. Vo, D.

C. Bondoc, J. Hall, W. W. Zhong, A. M. Sdicu, J. Davies, F. M. Klis, P. W. Robbins,

and H. Bussey. 1997. Large scale identification of genes involved in cell surface biosynthesis

and architecture in Saccharomyces cerevisiae. Genetics. 147:435-50.

119. Magee, B. B., and P. T. Magee. 2000. Induction of mating in Candida albicans by construction

of MTLa and MTLalpha strains. Science 289:310-3.

120. Marchetti, O., J. M. Entenza, D. Sanglard, J. Bille, M. P. Glauser, and P. Moreillon.

2000. Fluconazole plus cyclosporine: a fungicidal combination effective against experimental

endocarditis due to Candida albicans. Antimicrob Agents Chemother.

44:2932-8.

121. Marchetti, O., P. Moreillon, J. M. Entenza, J. Vouillamoz, M. P. Glauser, J. Bille, and

D. Sanglard. 2003. Fungicidal synergism of fluconazole and cyclosporine in Candida

albicans is not dependent on multidrug efflux transporters encoded by the CDR1,

CDR2, CaMDR1, and FLU1 genes. Antimicrob Agents Chemother. 47:1565-70.

122. Markovich, S., A. Yekutiel, I. Shalit, Y. Shadkchan, and N. Osherov. 2004. Genomic

approach to identification of mutations affecting caspofungin susceptibility in Saccharomyces

cerevisiae. Antimicrob Agents Chemother. 48:3871-6.

123. Marr, K. A., C. N. Lyons, T. R. Rustad, R. A. Bowden, and T. C. White. 1998. Rapid,

transient fluconazole resistance in Candida albicans is associated with increased

mRNA levels of CDR. Antimicrob Agents Chemother. 42:2584-9.

124. Marr, K. A., T. R. Rustad, J. H. Rex, and T. C. White. 1999. The trailing end point

phenotype in antifungal susceptibility testing is pH dependent. Antimicrob Agents

Chemother. 43:1383-6.

125. Marr, K. A., K. Seidel, M. A. Slavin, R. A. Bowden, H. G. Schoch, M. E. Flowers, L.

Corey, and M. Boeckh. 2000. Prolonged fluconazole prophylaxis is associated with

persistent protection against candidiasis-related death in allogeneic marrow transplant

recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood.

96:2055-61.

126. Martins, M. D., M. Lozano-Chiu, and J. H. Rex. 1998. Declining rates of oropharyngeal

candidiasis and carriage of Candida albicans associated with trends toward reduced

rates of carriage of fluconazole-resistant C. albicans in human immunodeficiency

virus-infected patients. Clin Infect Dis. 27:1291-4.

127. Mazur, P., N. Morin, W. Baginsky, M. el-Sherbeini, J. A. Clemas, J. B. Nielsen, and

F. Foor. 1995. Differential expression and function of two homologous subunits of

yeast 1,3-beta-D-glucan synthase. Mol Cell Biol. 15:5671-81.

128. Mille, C., G. Janbon, F. Delplace, S. Ibata-Ombetta, C. Gaillardin, G. Strecker, T. Jouault,

P. A. Trinel, and D. Poulain. 2004. Inactivation of CaMIT1 inhibits Candida albicans

phospholipomannan beta-mannosylation, reduces virulence, and alters cell wall

protein beta-mannosylation. J Biol Chem. 279:47952-60. Epub 2004 Sep 3.

98

129. 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. 110:293-302.

130. Mingot, J. M., E. A. Espeso, E. Diez, and M. A. Penalva. 2001. Ambient pH signaling

regulates nuclear localization of the Aspergillus nidulans PacC transcription factor.

Mol Cell Biol. 21:1688-99.

131. Mio, T., M. Adachi-Shimizu, Y. Tachibana, H. Tabuchi, S. B. Inoue, T. Yabe, T. Yamada-

Okabe, M. Arisawa, T. Watanabe, and H. Yamada-Okabe. 1997a. Cloning of

the Candida albicans homolog of Saccharomyces cerevisiae GSC1/FKS1 and its involvement

in beta-1,3-glucan synthesis. J Bacteriol 179:4096-105.

132. Mio, T., T. Yamada-Okabe, T. Yabe, T. Nakajima, M. Arisawa, and H. Yamada-

Okabe. 1997b. Isolation of the Candida albicans homologs of Saccharomyces cerevisiae

KRE6 and SKN1: expression and physiological function. J Bacteriol 179:2363-72.

133. Monge, R. A., E. Roman, C. Nombela, and J. Pla. 2006. The MAP kinase signal transduction

network in Candida albicans. Microbiology. 152:905-12.

134. Monod, M., and Z. M. Borg-von. 2002. Secreted aspartic proteases as virulence

factors of Candida species. Biol Chem. 383:1087-93.

135. Moore, R., T. 1998. in “The yeasts : a taxonomic study” Kutzman CP, Fell JW .Ed Elsevier,

Amsterdam. p33-44.

136. Morgan, J. 2005. Global trends in candidemia: review of reports from 1995-2005.

Curr Infect Dis Rep. 7:429-39.

137. Mouyna, I., T. Fontaine, M. Vai, M. Monod, W. A. Fonzi, M. Diaquin, L. Popolo, R.

P. Hartland, and J. P. Latge. 2000. Glycosylphosphatidylinositol-anchored glucanosyltransferases

play an active role in the biosynthesis of the fungal cell wall. J Biol Chem

275:14882-9.

138. Munro, C. A., R. K. Whitton, H. B. Hughes, M. Rella, S. Selvaggini, and N. A. Gow.

2003. CHS8-a fourth chitin synthase gene of Candida albicans contributes to in vitro

chitin synthase activity, but is dispensable for growth. Fungal Genet Biol 40:146-58.

139. Munro, C. A., K. Winter, A. Buchan, K. Henry, J. M. Becker, A. J. Brown, C. E. Bulawa,

and N. A. Gow. 2001. Chs1 of Candida albicans is an essential chitin synthase

required for synthesis of the septum and for cell integrity. Mol Microbiol 39:1414-26.

140. Navarro-Garcia, F., R. Alonso-Monge, H. Rico, J. Pla, R. Sentandreu, and C.

Nombela. 1998. A role for the MAP kinase gene MKC1 in cell wall construction and

morphological transitions in Candida albicans. Microbiology. 144:411-24.

141. Navarro-Garcia, F., B. Eisman, S. M. Fiuza, C. Nombela, and J. Pla. 2005. The MAP

kinase Mkc1p is activated under different stress conditions in Candida albicans.

Microbiology. 151:2737-49.

99

142. Navarro-Garcia, F., M. Sanchez, J. Pla, and C. Nombela. 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. 15:2197-206.

143. Nickas, M. E., and M. P. Yaffe. 1996. BRO1, a novel gene that interacts with components

of the Pkc1p-mitogen-activated protein kinase pathway in Saccharomyces

cerevisiae. Mol Cell Biol. 16:2585-93.

144. Niimi, K., K. Maki, F. Ikeda, A. R. Holmes, E. Lamping, M. Niimi, B. C. Monk, and

R. D. Cannon. 2006. Overexpression of Candida albicans CDR1, CDR2, or MDR1

does not produce significant changes in echinocandin susceptibility. Antimicrob

Agents Chemother. 50:1148-55.

145. NNIS, N. N. N. I. S. s. r. 2002. Data summary from January 1992-june 2001. Am J Infect

Control 2002 29:404-421.

146. 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. 41:196-9.

147. Odds, E. C. 1997. Switch of phenotype as an escape mechanism of the intruder. Mycoses.

40:9-12.

148. Odorizzi, G., D. J. Katzmann, M. Babst, A. Audhya, and S. D. Emr. 2003. Bro1 is an

endosome-associated protein that functions in the MVB pathway in Saccharomyces

cerevisiae. J Cell Sci. 116:1893-903. Epub 2003 Mar 18.

149. Osherov, N., Yekutiel A, Markowitz S, Shalit I, Shakdhan Y. 2003. A chemical genomics

approach towards identification of mutants affecting resistance to Caspofungin

in Saccharomyces cerevisiae., 43rd Interescience Conference of Antimicrobial Agents

and Chemotherapy. , Chicago, IL, .

150. Osherov, N., G. S. May, N. D. Albert, and D. P. Kontoyiannis. 2002. Overexpression

of Sbe2p, a Golgi protein, results in resistance to caspofungin in Saccharomyces

cerevisiae. Antimicrob Agents Chemother. 46:2462-9.

151. Papon, N., T. Noel, M. Florent, S. Gibot-Leclerc, D. Jean, C. Chastin, J. Villard, and

F. Chapeland-Leclerc. 2006. Molecular mechanism of flucytosine resistance in Candida

lusitaniae: Contribution of the FCY2, FCY1 and FUR1 genes to 5-fluorouracil

and fluconazole cross-resistance. Antimicrob Agents Chemother 23:23.

152. Parsons, A. B., R. L. Brost, H. Ding, Z. Li, C. Zhang, B. Sheikh, G. W. Brown, P. M.

Kane, T. R. Hughes, and C. Boone. 2004. Integration of chemical-genetic and genetic

interaction data links bioactive compounds to cellular target pathways. Nat Biotechnol

22:62-9.

153. Patterson, T. F. 2005. Advances and challenges in management of invasive mycoses.

Lancet 366:1013-25.

100

154. 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

Microbiol 58:425-51.

155. Penalva, M. A., and H. N. Arst, Jr. 2002. Regulation of gene expression by ambient

pH in filamentous fungi and yeasts. Microbiol Mol Biol Rev 66:426-46, table of contents.

156. Perea, S., J. L. Lopez-Ribot, W. R. Kirkpatrick, R. K. McAtee, R. A. Santillan, M.

Martinez, D. Calabrese, D. Sanglard, and T. F. Patterson. 2001. Prevalence of molecular

mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying

high-level fluconazole resistance isolated from human immunodeficiency virus-

infected patients. Antimicrob Agents Chemother. 45:2676-84.

157. Pittet, D., and R. P. Wenzel. 1995. Nosocomial bloodstream infections. Secular trends

in rates, mortality, and contribution to total hospital deaths. Arch Intern Med.

155:1177-84.

158. Podust, L. M., T. L. Poulos, and M. R. Waterman. 2001. Crystal structure of cytochrome

P450 14alpha -sterol demethylase (CYP51) from Mycobacterium tuberculosis

in complex with azole inhibitors. Proc Natl Acad Sci U S A. 98:3068-73.

159. Porta, A., A. M. Ramon, and W. A. Fonzi. 1999. PRR1, a homolog of Aspergillus nidulans

palF, controls pH-dependent gene expression and filamentation in Candida albicans.

J Bacteriol. 181:7516-23.

160. Poulain, D., C. Slomianny, T. Jouault, J. M. Gomez, and P. A. Trinel. 2002. Contribution

of phospholipomannan to the surface expression of beta-1,2-oligomannosides in

Candida albicans and its presence in cell wall extracts. Infect Immun 70:4323-8.

161. Ramon, A. M., and W. A. Fonzi. 2003. Diverged binding specificity of Rim101p, the

Candida albicans ortholog of PacC. Eukaryot Cell. 2:718-28.

162. Ramon, A. M., A. Porta, and W. A. Fonzi. 1999. Effect of environmental pH on morphological

development of Candida albicans is mediated via the PacC-related transcription

factor encoded by PRR2. J Bacteriol. 181:7524-30.

163. Reinoso-Martin, C., C. Schuller, M. Schuetzer-Muehlbauer, and K. Kuchler. 2003.

The yeast protein kinase C cell integrity pathway mediates tolerance to the antifungal

drug caspofungin through activation of Slt2p mitogen-activated protein kinase signaling.

Eukaryot Cell. 2:1200-10.

164. Revankar, S. G., W. R. Kirkpatrick, R. K. McAtee, O. P. Dib, A. W. Fothergill, S. W.

Redding, M. G. Rinaldi, and T. F. Patterson. 1996. Detection and significance of fluconazole

resistance in oropharyngeal candidiasis in human immunodeficiency virus-infected

patients. J Infect Dis. 174:821-7.

165. Rex, J. H., and M. A. Pfaller. 2002. Has antifungal susceptibility testing come of age?

Clin Infect Dis. 35:982-9. Epub 2002 Sep 24.

101

166. Richard, M., S. Ibata-Ombetta, F. Dromer, F. Bordon-Pallier, T. Jouault, and C. Gaillardin.

2002. Complete glycosylphosphatidylinositol anchors are required in Candida

albicans for full morphogenesis,