Strukturelle und funktionelle Charakterisierung der epithelialen Adhäsine aus Candida glabrata

Der humanpathogene Pilz Candida glabrata ist ein opportunistischer Erreger, der bevorzugt die Schleimhäute von Säugetieren besiedelt. C. glabrata ist für etwa 15 % der Blutstrominfektionen bei Menschen verantwortlich und verursacht besonders bei immunsupprimierten Patienten schwere Infektionsverläuf...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
1. Verfasser: Diderrich, Rike
Beteiligte: Mösch, Hans-Ulrich (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Veröffentlicht: Philipps-Universität Marburg 2014
Online Zugang:PDF-Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!

1. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685.


3. O'Toole GA, Pratt LA, Watnick PI, Newman DK, Weaver VB & Kolter R (1999) Genetic approaches to study of biofilms. Methods Enzymol 310: 91-109.

4. Sheehan JK, Kesimer M & Pickles R (2006) Innate immunity and mucus structure and function. Novartis Found Symp 279: 155-166; discussion 167-159, 216-159.

5. Bendtsen JD, Nielsen H, von Heijne G & Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340: 783-795.

6. Walker LA, Gow NA & Munro CA (2010) Fungal echinocandin resistance. Fungal Genet Biol 47: 117-126.

7. Kolbinger A, Gao T, Brock D, et al. (2005) A cysteine-rich extracellular protein containing a PA14 domain mediates quorum sensing in Dictyostelium discoideum. Eukaryot Cell 4: 991- 998.

8. Sandven P (2000) Epidemiology of candidemia. Rev Iberoam Micol 17: 73-81.

9. Ghannoum MA (1999) Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev 12: 501-517.

10. de Groot PW, Kraneveld EA, Yin QY, et al. (2008) The cell wall of the human pathogen Candida glabrata: differential incorporation of novel adhesin-like wall proteins. Eukaryot Cell 7: 1951-1964.

11. Pfaller MA & Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20: 133-163.

12. Chaffin WL, Lopez-Ribot JL, Casanova M, Gozalbo D & Martinez JP (1998) Cell wall and secreted proteins of Candida albicans: identification, function, and expression. Microbiol Mol Biol Rev 62: 130-180.

13. Ferrari S, Ischer F, Calabrese D, et al. (2009) Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog 5: e1000268.

14. Srikantha T, Daniels KJ, Wu W, et al. (2008) Dark brown is the more virulent of the switch phenotypes of Candida glabrata. Microbiology 154: 3309-3318.

15. Cowen LE & Steinbach WJ (2008) Stress, drugs, and evolution: the role of cellular signaling in fungal drug resistance. Eukaryot Cell 7: 747-764.

16. Pappas PG, Kauffman CA, Andes D, et al. (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48: 503-535.

17. Baker NA, Sept D, Joseph S, Holst MJ & McCammon JA (2001) Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci U S A 98: 10037-10041.

18. Zepelin B-v (2007) Epidemiology and antifungal susceptibilities of Candida spp. to six antifungal agents: results from a surveillance study on fungaemia in Germany from July 2004 to August 2005 Journal of Antimicrobial Chemotherapy 60: 424-428.

19. Hoyer LL, Payne TL & Hecht JE (1998) Identification of Candida albicans ALS2 and ALS4 and localization of als proteins to the fungal cell surface. J Bacteriol 180: 5334-5343.

20. Hibbett DS, Binder M, Bischoff JF, et al. (2007) A higher-level phylogenetic classification of the Fungi. Mycol Res 111: 509-547.

21. Cavalieri D, McGovern PE, Hartl DL, Mortimer R & Polsinelli M (2003) Evidence for S. cerevisiae fermentation in ancient wine. J Mol Evol 57: S226-232.

22. O'Sullivan O, Suhre K, Abergel C, Higgins DG & Notredame C (2004) 3DCoffee: combining protein sequences and structures within multiple sequence alignments. J Mol Biol 340: 385-395.

23. Tortorano AM, Kibbler C, Peman J, Bernhardt H, Klingspor L & Grillot R (2006) Candidaemia in Europe: epidemiology and resistance. Int J Antimicrob Agents 27: 359-366.

24. Scherer SE & Muzny DM & Buhay CJ, et al. (2006) The finished DNA sequence of human chromosome 12. Nature 440: 346-351.

25. De Nobel JG, Klis FM, Ram A, Van Unen H, Priem J, Munnik T & Van Den Ende H (1991) Cyclic variations in the permeability of the cell wall of Saccharomyces cerevisiae. Yeast 7: 589- 598.

26. Fleet GH (1985) Composition and structure of yeast cell walls. Curr Top Med Mycol 1: 24-56.

27. Kingsman AJ, Stanway C & Kingsman SM (1987) The expression of homologous and heterologous genes in yeast. Antonie Van Leeuwenhoek 53: 325-333.

28. Guery BP, Arendrup MC, Auzinger G, et al. (2009) Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment. Intensive Care Med 35: 206-214.

29. Sandven P, Giercksky KE, Group N & the Norwegian Yeast Study G (2001) Yeast colonization in surgical patients with intra-abdominal perforations. Eur J Clin Microbiol Infect Dis 20: 475- 481.

30. Bennett J & Scott KJ (1971) Quantitative staining of fraction I protein in polyacrylamide gels using Coomassie brillant blue. Anal Biochem 43: 173-182.

31. McPherson A (1982) Preparation and analysis of protein crystals.

32. Brown AJ (1992) Monitoring polysaccharide synthesis in Candida albicans. Carbohydr Res 227: 195-202.

33. Soll DR (1988) High-frequency switching in Candida albicans and its relations to vaginal candidiasis. Am J Obstet Gynecol 158: 997-1001.

34. Gonzalez M (2009) Glycoconjugate structure and function in fungal cell walls.

35. Casadevall A (2005) Fungal virulence, vertebrate endothermy, and dinosaur extinction: is there a connection? Fungal Genet Biol 42: 98-106.

36. Filler SG (2006) Candida-host cell receptor-ligand interactions. Curr Opin Microbiol 9: 333- 339.

37. Nguyen MH, Peacock JE, Jr., Morris AJ, et al. (1996) The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 100: 617-623.

38. Sobel JD, Faro S, Force RW, et al. (1998) Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 178: 203-211.

39. Fukuda M (2002) Roles of mucin-type O-glycans in cell adhesion. Biochim Biophys Acta 1573: 394-405.

40. Kapteyn JC, Van Den Ende H & Klis FM (1999) The contribution of cell wall proteins to the organization of the yeast cell wall. Biochim Biophys Acta 1426: 373-383.

41. Krcmery V (1999) Torulopsis glabrata an emerging yeast pathogen in cancer patients. Int J Antimicrob Agents 11: 1-6.

42. Yoshida E, Hidaka M, Fushinobu S, et al. (2010) Role of a PA14 domain in determining substrate specificity of a glycoside hydrolase family 3 beta-glucosidase from Kluyveromyces marxianus. Biochem J 431: 39-49.

43. Larsbrink J, Izumi A, Ibatullin FM, Nakhai A, Gilbert HJ, Davies GJ & Brumer H (2011) Structural and enzymatic characterization of a glycoside hydrolase family 31 alpha-xylosidase from Cellvibrio japonicus involved in xyloglucan saccharification. Biochem J 436: 567-580.

44. Aguilar-Uscanga B & Francois JM (2003) A study of the yeast cell wall composition and structure in response to growth conditions and mode of cultivation. Lett Appl Microbiol 37: 268- 274.

45. Naglik JR, Rodgers CA, Shirlaw PJ, et al. (2003) Differential expression of Candida albicans secreted aspartyl proteinase and phospholipase B genes in humans correlates with active oral and vaginal infections. J Infect Dis 188: 469-479.

46. Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN & Wenzel RP (1999) Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 29: 239-244.

47. Mundy RD & Cormack B (2009) Expression of Candida glabrata adhesins after exposure to chemical preservatives. J Infect Dis 199: 1891-1898.

48. de Hoon MJ, Imoto S, Nolan J & Miyano S (2004) Open source clustering software. Bioinformatics 20: 1453-1454.

49. Saldanha AJ (2004) Java Treeview--extensible visualization of microarray data. Bioinformatics 20: 3246-3248.

50. Larkin MA, Blackshields G, Brown NP, et al. (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23: 2947-2948.

51. Russo CL, Spurr-Michaud S, Tisdale A, Pudney J, Anderson D & Gipson IK (2006) Mucin gene expression in human male urogenital tract epithelia. Hum Reprod 21: 2783-2793.

52. Lagow E, DeSouza MM & Carson DD (1999) Mammalian reproductive tract mucins. Hum Reprod Update 5: 280-292.

53. De Las Penas A, Pan SJ, Castano I, Alder J, Cregg R & Cormack BP (2003) Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1-and SIR-dependent transcriptional silencing. Genes Dev 17: 2245-2258.

54. Leslie AG, Powell HR, Winter G, et al. (2002) Automation of the collection and processing of X-ray diffraction data --a generic approach. Acta Crystallogr D Biol Crystallogr 58: 1924- 1928.

55. Munshi S, Chen Z, Li Y, Olsen DB, Fraley ME, Hungate RW & Kuo LC (1998) Rapid X-ray diffraction analysis of HIV-1 protease-inhibitor complexes: inhibitor exchange in single crystals of the bound enzyme. Acta Crystallogr D Biol Crystallogr 54: 1053-1060.

56. Verstrepen KJ & Klis FM (2006) Flocculation, adhesion and biofilm formation in yeasts. Mol Microbiol 60: 5-15.

57. de Groot PW & Klis FM (2008) The conserved PA14 domain of cell wall-associated fungal adhesins governs their glycan-binding specificity. Mol Microbiol 68: 535-537.

58. Ruhnke M, Hartwig K & Kofla G (2008) New options for treatment of candidaemia in critically ill patients. Clin Microbiol Infect 14: 46-54.

59. Kuhn DM & Vyas VK (2012) The Candida glabrata adhesin Epa1p causes adhesion, phagocytosis, and cytokine secretion by innate immune cells. FEMS Yeast Res 12: 398-414.

60. Brückner S & Mösch HU (2012) Choosing the right lifestyle: adhesion and development in Saccharomyces cerevisiae. FEMS Microbiol Rev 36: 25-58.

61. Domergue R, Castano I, De Las Penas A, et al. (2005) Nicotinic acid limitation regulates silencing of Candida adhesins during UTI. Science 308: 866-870.

62. R. P (2004) Molecular Basis of Antifungal Resistance.

63. Verstrepen KJ & Fink GR (2009) Genetic and epigenetic mechanisms underlying cell-surface variability in protozoa and fungi. Annu Rev Genet 43: 1-24.

64. Braman J, Papworth C & Greener A (1996) Site-directed mutagenesis using double-stranded plasmid DNA templates. Methods Mol Biol 57: 31-44.

65. Zirkel J, Klinker H, Kuhn A, et al. (2012) Epidemiology of Candida blood stream infections in patients with hematological malignancies or solid tumors. Med Mycol 50: 50-55.

66. Douglas LJ (2003) Candida biofilms and their role in infection. Trends Microbiol 11: 30-36.

67. Ramage G, Martinez JP & Lopez-Ribot JL (2006) Candida biofilms on implanted biomaterials: a clinically significant problem. FEMS Yeast Res 6: 979-986.

68. Douglas LJ (2002) Medical importance of biofilms in Candida infections. Rev Iberoam Micol 19: 139-143.

69. Petosa C, Collier RJ, Klimpel KR, Leppla SH & Liddington RC (1997) Crystal structure of the anthrax toxin protective antigen. Nature 385: 833-838.

70. da Silva WJ, Goncalves LM, Seneviratne J, Parahitiyawa N, Samaranayake LP & Del Bel Cury AA (2012) Exopolysaccharide matrix of developed Candida albicans biofilms after exposure to antifungal agents. Braz Dent J 23: 716-722.

71. Klis FM, Mol P, Hellingwerf K & Brul S (2002) Dynamics of cell wall structure in Saccharomyces cerevisiae. FEMS Microbiol Rev 26: 239-256.

72. Wong S, Fares MA, Zimmermann W, Butler G & Wolfe KH (2003) Evidence from comparative genomics for a complete sexual cycle in the 'asexual' pathogenic yeast Candida glabrata. Genome Biol 4: R10.

73. Dieterich C, Schandar M, Noll M, Johannes FJ, Brunner H, Graeve T & Rupp S (2002) In vitro reconstructed human epithelia reveal contributions of Candida albicans EFG1 and CPH1 to adhesion and invasion. Microbiology 148: 497-506.

74. Netea MG, Brown GD, Kullberg BJ & Gow NA (2008) An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol 6: 67-78.

75. Mülhardt C (2002) Der Experimentator: Molekularbiologie, Genomics. Spektrum, Akad. Verl.

76. Lupetti A, Danesi R, Campa M, Del Tacca M & Kelly S (2002) Molecular basis of resistance to azole antifungals. Trends Mol Med 8: 76-81.

77. MacCallum DM, Castillo L, Nather K, Munro CA, Brown AJ, Gow NA & Odds FC (2009) Property differences among the four major Candida albicans strain clades. Eukaryot Cell 8: 373-387.

78. Goossens K & Willaert R (2010) Flocculation protein structure and cell-cell adhesion mechanism in Saccharomyces cerevisiae. Biotechnol Lett 32: 1571-1585.

79. Brunger AT (1992) Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 355: 472-475.

80. Bouchara JP, Zouhair R, Le Boudouil S, et al. (2000) In-vivo selection of an azole-resistant petite mutant of Candida glabrata. J Med Microbiol 49: 977-984.

81. Wilson HA, Jr., Downes TR, Julian JS, White WL & Haponik EF (1993) Candida endocarditis. A treatable form of pacemaker infection. Chest 103: 283-284.

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

83. Cormack BP, Ghori N & Falkow S (1999) An adhesin of the yeast pathogen Candida glabrata mediating adherence to human epithelial cells. Science 285: 578-582.

84. Lee KL, Buckley HR & Campbell CC (1975) An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida albicans. Sabouraudia 13: 148-153.

85. Odds FC, Brown AJ & Gow NA (2003) Antifungal agents: mechanisms of action. Trends Microbiol 11: 272-279.

86. Nett JE, Andes D.R (2012) Antifungals: drug class, mechanisms od action, pharmacokinetics/ pharmacodynamics, drug-drug interactions, toxicity, and clinical use. Candida and Candidiasis 345-371.

87. Tottrup HV & Carlsen S (1990) A process for the production of human proinsulin in Saccharomyces cerevisiae. Biotechnol Bioeng 35: 339-348.

88. Morris RJ, Perrakis, A. & Lamzin, V.S. (2003) ARP/wARP and automatic interpretation of protein electron density maps. Methods in enzymology 374: 229-244.

89. Kaur R, Domergue R, Zupancic ML & Cormack BP (2005) A yeast by any other name: Candida glabrata and its interaction with the host. Curr Opin Microbiol 8: 378-384.

90. Reynolds TB & Fink GR (2001) Bakers' yeast, a model for fungal biofilm formation. Science 291: 878-881.

91. Nett J, Lincoln L, Marchillo K & Andes D (2007) Beta -1,3 glucan as a test for central venous catheter biofilm infection. J Infect Dis 195: 1705-1712.

92. Gill SC & von Hippel PH (1989) Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem 182: 319-326.

93. Dolan JW, Bell AC, Hube B, Schaller M, Warner TF & Balish E (2004) Candida albicans PLD I activity is required for full virulence. Med Mycol 42: 439-447.

94. Vargas K, Srikantha R, Holke A, Sifri T, Morris R & Joly S (2004) Candida albicans switch phenotypes display differential levels of fitness. Med Sci Monit 10: BR198-206.

95. Odds FC (1988) Candida and Candidosis: A Review and Bibliography. Elsevier Science Health Science Division.

96. Klis FM, Boorsma A & De Groot PW (2006) Cell wall construction in Saccharomyces cerevisiae. Yeast 23: 185-202.

97. Cabib E, Blanco N, Grau C, Rodriguez-Pena JM & Arroyo J (2007) Crh1p and Crh2p are required for the cross-linking of chitin to beta(1-6)glucan in the Saccharomyces cerevisiae cell wall. Mol Microbiol 63: 921-935.

98. Rhodes G (2006) Crystallography made crystal clear a guide for users of macromolecular models.

99. Nikawa H, Nishimura H, Hamada T, Kumagai H & Samaranayake LP (1997) Effects of dietary sugars and, saliva and serum on Candida bioflim formation on acrylic surfaces. Mycopathologia 139: 87-91.

100. Cregg JM, Tolstorukov I, Kusari A, Sunga J, Madden K & Chappell T (2009) Expression in the yeast Pichia pastoris. Methods Enzymol 463: 169-189.

101. Persönliches RIKE DIDERRICH Diplom Chemikerin Adresse: Ferdinandstraße 17 40599 Düsseldorf Geboren: 19.08.1983

102. Veelders M (2008) Flokkuline aus Saccharomyces cerevisiae: funktionelle und strukturelle Untersuchungen. Thesis.

103. Willocks L, Leen CL, Brettle RP, Urquhart D, Russell TB & Milne LJ (1991) Fluconazole resistance in AIDS patients. J Antimicrob Chemother 28: 937-939.

104. Komshian SV, Uwaydah AK, Sobel JD & Crane LR (1989) Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient: frequency, characteristics, and evaluation of factors influencing outcome. Rev Infect Dis 11: 379-390.

105. Porath J & Flodin P (1959) Gel filtration: a method for desalting and group separation. Nature 183: 1657-1659.

106. de Groot PW, Hellingwerf KJ & Klis FM (2003) Genome-wide identification of fungal GPI proteins. Yeast 20: 781-796.

107. Sherman F (1991) Getting started with yeast. Methods Enzymol. 194: 3-21.

108. Zupancic ML, Frieman M, Smith D, Alvarez RA, Cummings RD & Cormack BP (2008) Glycan microarray analysis of Candida glabrata adhesin ligand specificity. Mol Microbiol 68: 547-559. Lebenslauf 218

109. Gulia J, Aryal S, Saadlla H & Shorr AF (2010) Health care-associated candidemia--a distinct entity? J Hosp Med 5: 298-301.

110. Udenfriend S & Kodukula K (1995) How glycosylphosphatidylinositol-anchored membrane proteins are made. Annu Rev Biochem 64: 563-591.

111. DiMaio F, Terwilliger TC, Read RJ, et al. (2011) Improved molecular replacement by density- and energy-guided protein structure optimization. Nature 473: 540-543.

112. Gow NA, Knox Y, Munro CA & Thompson WD (2003) Infection of chick chorioallantoic membrane (CAM) as a model for invasive hyphal growth and pathogenesis of Candida albicans. Med Mycol 41: 331-338.

113. Sherman F (1986) Laboratory course manual for methods in yeast genetics. Methods in Yeast Genetics, Cold Spring Harbor Laboratory Press.

114. Moen MD, Lyseng-Williamson KA & Scott LJ (2009) Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs 69: 361-392.

115. Cappellaro C, Baldermann C, Rachel R & Tanner W (1994) Mating type-specific cell-cell recognition of Saccharomyces cerevisiae: cell wall attachment and active sites of a-and alpha- agglutinin. EMBO J 13: 4737-4744.

116. Casadevall A, Rosas AL & Nosanchuk JD (2000) Melanin and virulence in Cryptococcus neoformans. Curr Opin Microbiol 3: 354-358.

117. Porath J, Carlsson J, Olsson I & Belfrage G (1975) Metal chelate affinity chromatography, a new approach to protein fractionation. Nature 258: 598-599.

118. Greenfield NJ (1996) Methods to estimate the conformation of proteins and polypeptides from circular dichroism data. Anal Biochem 235: 1-10.

119. Frieman MB, McCaffery JM & Cormack BP (2002) Modular domain structure in the Candida glabrata adhesin Epa1p, a beta1,6 glucan-cross-linked cell wall protein. Mol Microbiol 46: 479- 492.

120. Ruiz-Herrera J, Elorza MV, Valentin E & Sentandreu R (2006) Molecular organization of the cell wall of Candida albicans and its relation to pathogenicity. FEMS Yeast Res 6: 14-29.

121. Gipson IK, Ho SB, Spurr-Michaud SJ, et al. (1997) Mucin genes expressed by human female reproductive tract epithelia. Biol Reprod 56: 999-1011.

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

123. Cereghino GP, Cereghino JL, Ilgen C & Cregg JM (2002) Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris. Curr Opin Biotechnol 13: 329-332.

124. Davies DR (1971) Protein Crystallization: Micro Techniques Involving Vapor Diffusion. Methods Enzymol 22: 266-269.

125. Wilkins MR, Gasteiger E, Bairoch A, Sanchez JC, Williams KL, Appel RD & Hochstrasser DF (1999) Protein identification and analysis tools in the ExPASy server. Methods Mol Biol 112: 531-552.

126. Qiagen (2012) NeXtal Composition Tables.

127. Qiagen The Screens -an introduction.

128. Murshudov GN, Vagin, A.A. & Dodson, E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta crystallographica. Section D, 53: 240-255.

129. Morschhäuser J (2003) Resistenzen und Resistenzmechanismen. Pharm Unserer Zeit 2: 124- 128.

130. Blumberg HM, Jarvis WR, Soucie JM, et al. (2001) Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey. Clin Infect Dis 33: 177-186.

131. Sanglard D, Ischer F & Bille J (2001) Role of ATP-binding-cassette transporter genes in high- frequency acquisition of resistance to azole antifungals in Candida glabrata. Antimicrob Agents Chemother 45: 1174-1183.

132. Mullis KB & Faloona FA (1987) Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol 155: 335-350.

133. Weig M, Jansch L, Gross U, De Koster CG, Klis FM & De Groot PW (2004) Systematic identification in silico of covalently bound cell wall proteins and analysis of protein- polysaccharide linkages of the human pathogen Candida glabrata. Microbiology 150: 3129- 3144.

134. Notredame C, Higgins DG & Heringa J (2000) T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol 302: 205-217.

135. Castano I, Pan SJ, Zupancic M, Hennequin C, Dujon B & Cormack BP (2005) Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata. Mol Microbiol 55: 1246-1258.

136. Collaborative Computational Project N (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50: 760-763.

137. Pardini G, De Groot PW, Coste AT, Karababa M, Klis FM, de Koster CG & Sanglard D (2006) The CRH family coding for cell wall glycosylphosphatidylinositol proteins with a predicted transglycosidase domain affects cell wall organization and virulence of Candida albicans. J Biol Chem 281: 40399-40411.

138. Bartman AE, Buisine MP, Aubert JP, et al. (1998) The MUC6 secretory mucin gene is expressed in a wide variety of epithelial tissues. J Pathol 186: 398-405.

139. Schroeder JA, Thompson MC, Gardner MM & Gendler SJ (2001) Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland. J Biol Chem 276: 13057-13064.

140. Perriere G & Gouy M (1996) WWW-query: an on-line retrieval system for biological sequence banks. Biochimie 78: 364-369.

141. Lachke SA, Joly S, Daniels K & Soll DR (2002) Phenotypic switching and filamentation in Candida glabrata. Microbiology 148: 2661-2674.

142. Birnboim HC & Doly J (1979) A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res 7: 1513-1523.

143. Csank C & Haynes K (2000) Candida glabrata displays pseudohyphal growth. FEMS Microbiol Lett 189: 115-120.

144. Kantarcioglu AS & Yucel A (2002) Phospholipase and protease activities in clinical Candida isolates with reference to the sources of strains. Mycoses 45: 160-165.

145. Iraqui I, Garcia-Sanchez S, Aubert S, Dromer F, Ghigo JM, d'Enfert C & Janbon G (2005) The Yak1p kinase controls expression of adhesins and biofilm formation in Candida glabrata in a Sir4p-dependent pathway. Mol Microbiol 55: 1259-1271.

146. Sobel JD (1988) Pathogenesis and epidemiology of vulvovaginal candidiasis. Ann N Y Acad Sci 544: 547-557.

147. Langfelder K, Streibel M, Jahn B, Haase G & Brakhage AA (2003) Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal Genet Biol 38: 143-158.

148. Mayser P, Wenzel M, Kramer HJ, Kindler BL, Spiteller P & Haase G (2007) Production of indole pigments by Candida glabrata. Med Mycol 45: 519-524.

149. Rigden DJ, Mello LV & Galperin MY (2004) The PA14 domain, a conserved all-beta domain in bacterial toxins, enzymes, adhesins and signaling molecules. Trends Biochem Sci 29: 335-339.

150. Battye TG, Kontogiannis L, Johnson O, Powell HR & Leslie AG (2011) iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr 67: 271-281.

151. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC & Read RJ (2007) Phaser crystallographic software. J Appl Crystallogr 40: 658-674.

152. Hattrup CL & Gendler SJ (2008) Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol 70: 431-457.

153. Steinkellner G, Rader R, Thallinger GG, Kratky C & Gruber K (2009) VASCo: computation and visualization of annotated protein surface contacts. BMC Bioinformatics 10: 32.

154. Nieuw Amerongen AV (1998) Sulfomucins in the human body. Biol Chem. 379: 1-18.

155. Kelly SM (2000) The use of circular dichroism in the investigation of protein structure and function. Curr. Protein Pept. Sci 1: 349-384.

156. Goffeau A, Barrell BG, Bussey H, et al. (1996) Life with 6000 genes. Science 274: 546, 563- 547.

157. Dodgson AR, Pujol C, Pfaller MA, Denning DW & Soll DR (2005) Evidence for recombination in Candida glabrata. Fungal Genet Biol 42: 233-243.

158. Nusbaum C, Mikkelsen TS, Zody MC, et al. (2006) DNA sequence and analysis of human chromosome 8. Nature 439: 331-335.

159. Eswar N, Webb B, Marti-Renom MA, et al. (2006) Comparative protein structure modeling using Modeller. Curr Protoc Bioinformatics Chapter 5: Unit 5 6.

160. Guarro J, GeneJ & Stchigel AM (1999) Developments in fungal taxonomy. Clin Microbiol Rev 12: 454-500.

161. Miyazaki H, Miyazaki Y, Geber A, et al. (1998) Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata. Antimicrob Agents Chemother 42: 1695-1701.

162. Moran GP, Sanglard D, Donnelly SM, Shanley DB, Sullivan DJ & Coleman DC (1998) Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrob Agents Chemother 42: 1819-1830.

163. Kobayashi O, Hayashi N, Kuroki R & Sone H (1998) Region of FLO1 proteins responsible for sugar recognition. J Bacteriol 180: 6503-6510.

164. Kumamoto CA (2002) Candida biofilms. Curr Opin Microbiol 5: 608-611.

165. Tanny JC & Moazed D (2001) Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product. Proc Natl Acad Sci U S A 98: 415-420.

166. Cormack BP & Falkow S (1999) Efficient homologous and illegitimate recombination in the opportunistic yeast pathogen Candida glabrata. Genetics 151: 979-987.

167. Braun BR & Johnson AD (2000) TUP1, CPH1 and EFG1 make independent contributions to filamentation in Candida albicans. Genetics 155: 57-67.

168. Verstrepen KJ, Jansen A, Lewitter F & Fink GR (2005) Intragenic tandem repeats generate functional variability. Nat Genet 37: 986-990.

169. Pfaller MA, Diekema DJ, Messer SA, Hollis RJ & Jones RN (2003) In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazole-resistant isolates. Antimicrob Agents Chemother 47: 1068-1071.

170. Knowles MR (2002) Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 109: 571-577.

171. Srikantha T, Lachke SA & Soll DR (2003) Three mating type-like loci in Candida glabrata. Eukaryot Cell 2: 328-340.

172. Saville SP, Lazzell AL, Bryant AP, et al. (2006) Inhibition of filamentation can be used to treat disseminated candidiasis. Antimicrob Agents Chemother 50: 3312-3316.

173. Marichal P, Vanden Bossche H, Odds FC, et al. (1997) Molecular biological characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother 41: 2229-2237.

174. Fridkin SK & Jarvis WR (1996) Epidemiology of nosocomial fungal infections. Clin Microbiol Rev 9: 499-511.

175. Guo B, Styles CA, Feng Q & Fink GR (2000) A Saccharomyces gene family involved in invasive growth, cell-cell adhesion, and mating. Proc Natl Acad Sci U S A 97: 12158-12163.

176. Popolo L, Gilardelli D, Bonfante P & Vai M (1997) Increase in chitin as an essential response to defects in assembly of cell wall polymers in the ggp1delta mutant of Saccharomyces cerevisiae. J Bacteriol 179: 463-469.

177. Kapteyn JC, Ram AF, Groos EM, et al. (1997) Altered extent of cross-linking of beta1,6- glucosylated mannoproteins to chitin in Saccharomyces cerevisiae mutants with reduced cell wall beta1,3-glucan content. J Bacteriol 179: 6279-6284.

178. Kaur R (2007) A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata. Proc Natl Acad Sci U S A 104: 7628–7633.

179. Hitchcock CA, Pye GW, Troke PF, Johnson EM & Warnock DW (1993) Fluconazole resistance in Candida glabrata. Antimicrob Agents Chemother 37: 1962-1965.

180. Tumbarello M, Posteraro B, Trecarichi EM, et al. (2007) Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J Clin Microbiol 45: 1843-1850.

181. Naglik JR, Challacombe SJ & Hube B (2003) Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol Mol Biol Rev 67: 400-428.

182. Odds FC, Rinaldi MG, Cooper CR, Jr., Fothergill A, Pasarell L & McGinnis MR (1997) Candida and Torulopsis: a blinded evaluation of use of pseudohypha formation as basis for identification of medically important yeasts. J Clin Microbiol 35: 313-316.

183. Eisen MB, Spellman PT, Brown PO & Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95: 14863-14868.

184. Hassell AM, An G, Bledsoe RK, et al. (2007) Crystallization of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr 63: 72-79.

185. Polakova S, Blume C, Zarate JA, Mentel M, Jorck-Ramberg D, Stenderup J & Piskur J (2009) Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata. Proc Natl Acad Sci U S A 106: 2688-2693.

186. Smith AE, Zhang Z, Thomas CR, Moxham KE & Middelberg AP (2000) The mechanical properties of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 97: 9871-9874.

187. Emsley P, et al. (2010) Features and development of Coot. . Acta crystallographica. Section D, Biological crystallography 66: 486-501.

188. Veelders M, Bruckner S, Ott D, Unverzagt C, Mosch HU & Essen LO (2010) Structural basis of flocculin-mediated social behavior in yeast. Proc Natl Acad Sci U S A 107: 22511-22516.

189. Xie X & Lipke PN (2010) On the evolution of fungal and yeast cell walls. Yeast 27: 479-488.

190. Brockert PJ, Lachke SA, Srikantha T, Pujol C, Galask R & Soll DR (2003) Phenotypic switching and mating type switching of Candida glabrata at sites of colonization. Infect Immun 71: 7109-7118.

191. Pfaller MA, Messer SA, Boyken L, Rice C, Tendolkar S, Hollis RJ & Diekema DJ (2003) Caspofungin activity against clinical isolates of fluconazole-resistant Candida. J Clin Microbiol 41: 5729-5731.

192. Salgado PS, Yan R, Taylor JD, et al. (2011) Structural basis for the broad specificity to host-cell ligands by the pathogenic fungus Candida albicans. Proc Natl Acad Sci U S A 108: 15775- 15779.

193. Desai C, Mavrianos J & Chauhan N (2011) Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial cells. FEMS Yeast Res 11: 595-601.

194. Maestre-Reyna M, Diderrich R, Veelders MS, et al. (2012) Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia. Proc Natl Acad Sci U S A 109: 16864-16869.

195. de Groot PW, Bader O, de Boer AD, Weig M & Chauhan N (2013) Adhesins in human fungal pathogens: glue with plenty of stick. Eukaryot Cell 12: 470-481.

196. Lipke PN & Kurjan J (1992) Sexual agglutination in budding yeasts: structure, function, and regulation of adhesion glycoproteins. Microbiol Rev 56: 180-194.

197. Vogelstein B & Gillespie D (1979) Preparative and analytical purification of DNA from agarose. Proc Natl Acad Sci U S A 76: 615-619.

198. Hajjeh RA, Sofair AN, Harrison LH, et al. (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: 1519-1527.

199. Hinnen A, Hicks JB & Fink GR (1978) Transformation of yeast. Proc Natl Acad Sci U S A 75: 1929-1933.

200. de Groot PW, de Boer AD, Cunningham J, et al. (2004) Proteomic analysis of Candida albicans cell walls reveals covalently bound carbohydrate-active enzymes and adhesins. Eukaryot Cell 3: 955-965.

201. Blixt O, Head S, Mondala T, et al. (2004) Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc Natl Acad Sci U S A 101: 17033-17038.

202. Fidel PL, Jr., Vazquez JA & Sobel JD (1999) Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev 12: 80- 96.

203. Ghannoum MA (2000) Potential role of phospholipases in virulence and fungal pathogenesis. Clin Microbiol Rev 13: 122-143.

204. Sanglard D, Ischer F, Calabrese D, Majcherczyk PA & Bille J (1999) The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob Agents Chemother 43: 2753-2765.

205. Henry KW, Nickels JT & Edlind TD (2000) Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother 44: 2693-2700.

206. Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T & Ghannoum MA (2001) Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 183: 5385-5394.

207. Lachke SA, Srikantha T, Tsai LK, Daniels K & Soll DR (2000) Phenotypic switching in Candida glabrata involves phase-specific regulation of the metallothionein gene MT-II and the newly discovered hemolysin gene HLP. Infect Immun 68: 884-895.

208. DeLano WL (2002) The PyMOL molecular graphics system. ed.^eds.), p.^pp.

209. van der Vaart JM, van Schagen FS, Mooren AT, Chapman JW, Klis FM & Verrips CT (1996) The retention mechanism of cell wall proteins in Saccharomyces cerevisiae. Wall-bound Cwp2p is beta-1,6-glucosylated. Biochim Biophys Acta 1291: 206-214.

210. Osumi M (1998) The ultrastructure of yeast: cell wall structure and formation. Micron 29: 207- 233.

211. Bergfors T (2003) Seeds to crystals. J Struct Biol 142: 66-76.

212. Dujon B, Sherman D, Fischer G, et al. (2004) Genome evolution in yeasts. Nature 430: 35-44.

213. Naglik JR, Albrecht A, Bader O & Hube B (2004) Candida albicans proteinases and host/pathogen interactions. Cell Microbiol 6: 915-926.

214. Verstrepen KJ, Reynolds TB & Fink GR (2004) Origins of variation in the fungal cell surface. Nat Rev Microbiol 2: 533-540.