Molecular Basis of Fungal Adherence to Endothelial and Epithelial Cells

Scott G. Filler; Donald C. Sheppard; John E. Edwards, Jr.

doi:10.1128/9781555815776.ch13

Chapter 13 : Molecular Basis of Fungal Adherence to Endothelial and Epithelial Cells

Authors: Scott G. Filler¹, Donald C. Sheppard², John E. Edwards, Jr.³

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and the David Geffen School of Medicine at UCLA, Los Angeles, California; 2: Departments of Microbiology and Immunology, Medicine, McGill University, Montreal, Quebec, Canada; 3: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and the David Geffen School of Medicine at UCLA, Los Angeles, California

Content Type: Monograph

Publication Year: 2006

Category: Fungi and Fungal Pathogenesis

Book DOI: 10.1128/9781555815776

Chapter DOI: 10.1128/9781555815776.ch13

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

Preview this chapter:

Molecular Basis of Fungal Adherence to Endothelial and Epithelial Cells, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap13-1.gif /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap13-2.gif

Abstract:

This chapter focuses on fungal adhesins that have been characterized at the genetic level and that mediate adherence to host constituents. These adhesins include Als proteins, Hwp1p, Eap1p, Csh1p, and other less well characterized proteins. ALS1 is part of a gene family that is characterized by the presence of conserved tandem repeats. The ALS gene family contains at least eight members, ALS1, ALS2, ALS3, ALS4, ALS5, ALS6, ALS7, and ALS9. A comprehensive study of the binding specificity of Als proteins expressed in Saccharomyces cerevisiae found that that Als1p, Als3p, and Als5p mediate adherence to a broad variety of host substrates, including endothelial cells, oral epithelial cells, collagen, fibronectin, and laminin. Fragments of genes with homology to the Candida albicans ALS gene family have been detected in Candida dubliniensis and Candida tropicalis. Several studies have demonstrated that Aspergillus fumigatus conidia and hyphae adhere specifically to a variety of host substrates including laminin, fibrinogen, fibronectin, and pulmonary epithelial cells. The identification and characterization of fungal adhesins have been greatly facilitated by the development of powerful molecular biology tools and the recently completed fungal genome-sequencing projects. Furthermore, many important fungal adhesins will probably be glycosylphosphatidylinositol (GPI)-linked proteins with serine- and threonine-rich tandem repeats in their central domains. Identification of these adhesins is important because it provides insight into the mechanisms of fungal pathogenicity, as well as potential therapeutic targets.

Citation: Filler S, Sheppard D, Edwards, Jr. J. 2006. Molecular Basis of Fungal Adherence to Endothelial and Epithelial Cells, p 187-196. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch13

Highlighted Text: Show | Hide

Full text loading...

Figures

Molecular Basis of Fungal Adherence to Endothelial and Epithelial Cells

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815776.ch13-1,webId=/content/author/10.1128/9781555815776.ch13-1,properties={foaf_givenname=Scott G., foaf_name=Scott G. Filler, foaf_surname=Filler, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815776.ch13-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815776.ch13-2,webId=/content/author/10.1128/9781555815776.ch13-2,properties={foaf_givenname=Donald C., foaf_name=Donald C. Sheppard, foaf_surname=Sheppard, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815776.ch13-aff2]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815776.ch13-3,webId=/content/author/10.1128/9781555815776.ch13-3,properties={foaf_givenname=John E., foaf_name=John E. Edwards, Jr., foaf_surname=Edwards, Jr., pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815776.ch13-aff3]]}]]

/content/10.1128/9781555815776.ch13.ch13fig01

Figure 1.

Conceptual model of structure-function relationships in Als family proteins. Als proteins are composed of three general components: an N-terminal domain, serine/threonine-rich tandem repeats, and a serine/threonine-rich C-terminal domain containing a GPI anchor that is bound to the C. albicans cell wall. As illustrated, Als proteins contain multiple conserved antiparallel β-sheet regions (CR1–n) that are separated by extended spans, characteristic of the immunoglobulin superfamily. Projecting from the β-sheet domains are loop/coil structures containing the hypervariable regions (HVRs). The three-dimensional physicochemical properties of specific Als protein hypervariable regions probably govern interactions with host substrates that confer adhesive and invasive functions to C. albicans. For illustrative purposes, only three N-terminal β-sheet/coil domains and their respective conserved region and hypervariable region components are shown.

10.1128/9781555815776/f0188-01_thmb.gif

10.1128/9781555815776/f0188-01.gif

Figure 1.

References

/content/book/10.1128/9781555815776.ch13

1. Banerjee, B.,, P. A. Greenberger,, J. N. Fink, and, V. P. Kurup. 1998. Immunological characterization of Asp f 2, a major allergen from Aspergillus fumigatus associated with allergic bronchopulmonary aspergillosis. Infect. Immun. 66: 5175– 5182.

2. Belanger, P. H.,, D. Johnston,, R. A. Fratti,, M. Zhang, and, S. G. Filler. 2002. Endocytosis of Candida albicans by vascular endothelial cells is associated with tyrosine phosphorylation of specific host cell proteins. Cell. Microbiol. 4: 805– 812.

3. Bouchara, J. P.,, A. Bouali,, G. Tronchin,, R. Robert,, D. Chabasse, and, J. M. Senet. 1988. Binding of fibrinogen to the pathogenic Aspergillus species. J. Med. Vet. Mycol. 26: 327– 334.

4. Bouchara, J. P.,, M. Sanchez,, A. Chevailler,, A. Marot-Leblond,, J. C. Lissitzky,, G. Tronchin, and, D. Chabasse. 1997. Sialic acid-dependent recognition of laminin and fibrinogen by Aspergillus fumigatus conidia. Infect. Immun. 65: 2717– 2724.

5. Casanova, M.,, J. L. Lopez-Ribot,, C. Monteagudo,, A. Llombart-Bosch,, R. Sentandreu, and, J. P. Martinez. 1992. Identification of a 58-kilodalton cell surface fibrinogen-binding mannoprotein from Candida albicans. Infect. Immun. 60: 4221– 4229.

6. Chang, Y. C.,, M. F. Stins,, M. J. McCaffery,, G. F. Miller,, D. R. Pare,, T. Dam,, M. Paul-Satyasee,, K. S. Kim, and, K. J. Kwon-Chung. 2004. Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier. Infect. Immun. 72: 4985– 4995.

7. Chen, S. H.,, M. F. Stins,, S. H. Huang,, Y. H. Chen,, K. J. Kwon-Chung,, Y. Chang,, K. S. Kim,, K. Suzuki, and, A. Y. Jong. 2003. Cryptococcus neoformans induces alterations in the cytoskeleton of human brain microvascular endothelial cells. J. Med. Microbiol. 52: 961– 970.

8. Cheng, G.,, K. Wozniak,, M. A. Wallig,, P. L. Fidel, Jr.,, S. R. Trupin, and, L. L. Hoyer. 2005. Comparison between Candida albicans agglutinin-like sequence gene expression patterns in human clinical specimens and models of vaginal candidiasis. Infect. Immun. 73: 1656– 1663.

9. de Groot, P. W.,, A. D. de Boer,, J. Cunningham,, H. L. Dekker,, L. de Jong,, K. J. Hellingwerf,, C. de Koster, and, F. M. Klis. 2004. Proteomic analysis of Candida albicans cell walls reveals covalently bound carbohydrate-active enzymes and adhesins. Eukaryot. Cell 3: 955– 965.

10. DeHart, D. J.,, D. E. Agwu,, N. C. Julian, and, R. G. Washburn. 1997. Binding and germination of Aspergillus fumigatus conidia on cultured A549 pneumocytes. J. Infect. Dis. 175: 146– 150.

11. Filler, S. G.,, J. N. Swerdloff,, C. Hobbs, and, P. M. Luckett. 1995. Penetration and damage of endothelial cells by Candida albicans. Infect. Immun. 63: 976– 983.

12. 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: 61– 72.

13. Fu, Y.,, G. Rieg,, W. A. Fonzi,, P. H. Belanger,, J. E. Edwards, Jr., and, S. G. Filler. 1998. Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces adherence to endothelial and epithelial cells. Infect. Immun. 66: 1783– 1786.

14. Gale, C.,, D. Finkel,, N. Tao,, M. Meinke,, M. McClellan,, J. Olson,, K. Kendrick, and, M. Hostetter. 1996. Cloning and expression of a gene encoding an integrin-like protein in Candida albicans. Proc. Natl. Acad. Sci. USA 93: 357– 361.

15. Gale, C.,, M. Gerami-Nejad,, M. McClellan,, S. Vandoninck,, M. S. Longtine, and, J. Berman. 2001. Candida albicans Int1p interacts with the septin ring in yeast and hyphal cells. Mol. Biol. Cell 12: 3538– 3549.

16. 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: 1355– 1358.

17. Gaur, N. K., and, S. A. Klotz. 2004. Accessibility of the peptide backbone of protein ligands is a key specificity determinant in Candida albicans SRS adherence. Microbiology 150: 277– 284.

18. Gaur, N. K., and, S. A. Klotz. 1997. Expression, cloning, and characterization of a Candida albicans gene, ALA1, that confers adherence properties upon Saccharomyces cerevisiae for extracellular matrix proteins. Infect. Immun. 65: 5289– 5294.

19. Gaur, N. K.,, S. A. Klotz, and, R. L. Henderson. 1999. overexpression of the Candida albicans ALA1 gene in Saccharomyces cerevisiae results in aggregation following attachment of yeast cells to extracellular matrix proteins, adherence properties similar to those of Candida albicans. Infect. Immun. 67: 6040– 6047.

20. Gaur, N. K.,, R. L. Smith, and, S. A. Klotz. 2002. Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to accessible threonine, serine, or ala-nine patches. Cell Commun. Adhes. 9: 45– 57.

21. Gil, M. L.,, M. C. Penalver,, J. L. Lopez-Ribot,, J. E. O’Connor, and, J. P. Martinez. 1996. Binding of extracellular matrix proteins to Aspergillus fumigatus conidia. Infect. Immun. 64: 5239– 5247.

22. Glee, P. M.,, J. E. Cutler,, E. E. Benson,, R. F. Bargatze, and, K. C. Hazen. 2001. Inhibition of hydrophobic protein-mediated Candida albicans attachment to endothelial cells during physiologic shear flow. Infect. Immun. 69: 2815– 2820.

23. 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: 267– 275.

24. Green, C. B.,, X. Zhao, and, L. L. Hoyer. 2005. Use of green fluorescent protein and reverse transcription-PCR to monitor Candida albicans agglutinin-like sequence gene expression in a murine model of disseminated candidiasis. Infect. Immun. 73: 1852– 1855.

25. Green, C. B.,, X. Zhao,, K. M. Yeater, and, L. L. Hoyer. 2005. Construction and real-time RT-PCR validation of Candida albicans PALS-GFP reporter strains and their use in flow cytometry analysis of ALS gene expression in budding and filamenting cells. Microbiology 151: 1051– 1060.

26. 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– 1527.

27. Hamada, K.,, H. Terashima,, M. Arisawa,, N. Yabuki, and, K. Kitada. 1999. Amino acid residues in the omega-minus region participate in cellular localization of yeast glycosylphosphatidylinositol-attached proteins. J. Bacteriol. 181: 3886– 3889.

28. Hazen, K. C. 2004. Relationship between expression of cell surface hydrophobicity protein 1 (CSH1p) and surface hydrophobicity properties of Candida dubliniensis. Curr. Microbiol. 48: 447– 451.

29. 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– 4255.

30. 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: 1555– 1567.

31. Hoyer, L. L., and, J. E. Hecht. 2001. The ALS5 gene of Candida albicans and analysis of the Als5p N-terminal domain. Yeast 18: 49– 60.

32. Hoyer, L. L., and, J. E. Hecht. 2000. The ALS6 and ALS7 genes of Candida albicans. Yeast 16: 847– 855.

33. Hoyer, L. L.,, T. L. Payne,, M. Bell,, A. M. Myers, and, S. Scherer. 1998. Candida albicans ALS3 and insights into the nature of the ALS gene family. Clin. Microbiol. Rev. 33: 451– 459.

34. Hoyer, L. L.,, T. L. Payne, and, J. E. Hecht. 1998. Identification of Candida albicans ALS2 and ALS4 and localization of als proteins to the fungal cell surface. J. Bacteriol. 180: 5334– 5343.

35. Hoyer, L. L.,, S. Scherer,, A. R. Shatzman, and, G. P. Livi. 1995. Candida albicans ALS1 : domains related to a Saccharomyces cerevisiae sexual agglutinin separated by a repeating motif. Mol. Microbiol. 15: 39– 54.

36. Ibrahim, A. S.,, S. G. Filler,, M. S. Alcouloumre,, T. R. Kozel,, J. E. Edwards, Jr., and, M. A. Ghannoum. 1995. Adherence to and damage of endothelial cells by Cryptococcus neoformans in vitro: role of the capsule. Infect. Immun. 63: 4368– 4374.

37. Ibrahim, A. S.,, B. J. Spellberg,, V. Avenissian,, Y. Fu,, S. G. Filler, and, J. E. Edwards, Jr. 2005. Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect. Immun. 73: 999– 1005.

38. Kleinegger, C. L.,, S. R. Lockhart,, K. Vargas, and, D. R. Soll. 1996. Frequency, intensity, species, and strains of oral Candida vary as a function of host age. J. Clin. Microbiol. 34: 2246– 2254.

39. Klotz, S. A.,, N. K. Gaur,, D. F. Lake,, V. Chan,, J. Rauceo, and, P. N. Lipke. 2004. Degenerate peptide recognition by Candida albicans adhesins Als5p and Als1p. Infect. Immun. 72: 2029– 2034.

40. Klotz, S. A.,, M. L. Pendrak, and, R. C. Hein. 2001. Antibodies to alpha5beta1 and alpha(v)beta3 integrins react with Candida albicans alcohol dehydrogenase. Microbiology 147: 3159– 3164.

41. Klotz, S. A., and, R. L. Smith. 1991. A fibronectin receptor on Candida albicans mediates adherence of the fungus to extracellular matrix. J. Infect. Dis. 163: 604– 610.

42. Li, F., and, S. P. Palecek. 2003. EAP1, a Candida albicans gene involved in binding human epithelial cells. Eukaryot. Cell 2: 1266– 1273.

43. Lopez-Ribot, J. L.,, P. Sepulveda,, A. M. Cervera,, P. Roig,, D. Gozalbo, and, J. P. Martinez. 1997. Cloning of a cDNA fragment encoding part of the protein moiety of the 58-kDa fibrinogen-binding mannoprotein of Candida albicans. FEMS Microbiol. Lett. 157: 273– 278.

44. Loza, L.,, Y. Fu,, A. S. Ibrahim,, D. C. Sheppard,, S. G. Filler, and, J. E. Edwards, Jr. 2004. Functional analysis of the Candida albicans ALS1 gene product. Yeast 21: 473– 482.

45. Masuoka, J.,, G. Wu,, P. M. Glee, and, K. C. Hazen. 1999. Inhibition of Candida albicans attachment to extracellular matrix by antibodies which recognize hydrophobic cell wall proteins. FEMS Immunol. Med. Microbiol. 24: 421– 429.

46. Oh, S. H.,, G. Cheng,, J. A. Nuessen,, R. Jajko,, K. M. Yeater,, X. Zhao,, C. Pujol,, D. R. Soll, and, L. L. Hoyer. 2005. Functional specificity of Candida albicans Als3p proteins and clade specificity of ALS3 alleles discriminated by the number of copies of the tandem repeat sequence in the central domain. Microbiology 151: 673– 681.

47. Pfaller, M. A.,, R. N. Jones,, G. V. Doern,, H. S. Sader,, S. A. Messer,, A. Houston,, S. Coffman, and, R. J. Hollis. 2000. Bloodstream infections due to Candida species: SENTRY antimicrobial surveillance program in North America and Latin America, 1997–1998. Antimicrob. Agents Chemother. 44: 747– 751.

48. Phan, Q. T.,, P. H. Belanger, and, S. G. Filler. 2000. Role of hyphal formation in interactions of Candida albicans with endothelial cells. Infect. Immun. 68: 3485– 3490.

49. Phan, Q. T.,, R. A. Fratti,, N. V. Prasadarao,, J. E. Edwards, Jr., and, S. G. Filler. 2005. N-cadherin mediates endocytosis of Candida albicans by endothelial cells. J. Biol. Chem. 280: 10455– 10461.

50. Rauceo, J. M.,, N. K. Gaur,, K. G. Lee,, J. E. Edwards,, S. A. Klotz, and, P. N. Lipke. 2004. Global cell surface conformational shift mediated by a Candida albicans adhesin. Infect. Immun. 72: 4948– 4955.

51. Redding, S. W.,, R. C. Zellars,, W. R. Kirkpatrick,, R. K. McAtee,, M. A. Caceres,, A. W. Fothergill,, J. L. Lopez-Ribot,, C. W. Bailey,, M. G. Rinaldi, and, T. F. Patterson. 1999. Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer. J. Clin. Microbiol. 37: 3896– 3900.

52. Revankar, S. G.,, O. P. Dib,, W. R. Kirkpatrick,, R. K. McAtee,, A. W. Fothergill,, M. G. Rinaldi,, S. W. Redding, and, T. F. Patterson. 1998. Clinical evaluation and microbiology of oropharyngeal infection due to fluconazole-resistant Candida in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 26: 960– 963.

53. Rhodus, N. L.,, C. Bloomquist,, W. Liljemark, and, J. Bereuter. 1997. Prevalence, density, and manifestations of oral Candida albicans in patients with Sjogren’s syndrome. J. Otolaryngol. 26: 300– 305.

54. Richter, S. S.,, R. P. Galask,, S. A. Messer,, R. J. Hollis,, D. J. Diekema, and, M. A. Pfaller. 2005. Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J. Clin. Microbiol. 43: 2155– 2162.

55. Sanchez, A. A.,, D. A. Johnston,, C. Myers,, J. E. Edwards, Jr.,, A. P. Mitchell, and, S. G. Filler. 2004. Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and endothelial cell damage in vitro. Infect. Immun. 72: 598– 601.

56. Sangeorzan, J. A.,, S. F. Bradley,, X. He,, L. T. Zarins,, G. L. Ridenour,, R. N. Tiballi, and, C. A. Kauffman. 1994. Epidemiology of oral candidiasis in HIV-infected patients:colonization, infection, treatment, and emergence of fluconazole resistance. Am. J. Med. 97: 339– 346.

57. Santos, M. A.,, G. Keith, and, M. F. Tuite. 1993. Nonstandard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5’-CAG-3’ (leucine) anticodon. EMBO J. 12: 607– 616.

58. Santos, M. A., and, M. F. Tuite. 1995. The CUG codon is decoded in vivo as serine and not leucine in Candida albi-cans. Nucleic Acids Res. 23: 1481– 1486.

59. Segurado, M.,, R. Lopez-Aragon,, J. A. Calera,, J. M. Fernandez-Abalos, and, F. Leal. 1999. Zinc-regulated biosynthesis of immunodominant antigens from Aspergillus spp. Infect. Immun. 67: 2377– 2382.

60. Sentandreu, M.,, M. V. Elorza,, R. Sentandreu, and, W. A. Fonzi. 1998. Cloning and characterization of PRA1, a gene encoding a novel pH-regulated antigen of Candida albicans. J. Bacteriol. 180: 282– 289.

61. Sharkey, L. L.,, W. L. Liao,, A. K. Ghosh, and, W. A. Fonzi. 2005. Flanking direct repeats of hisG alter URA3 marker expression at the HWP1 locus of Candida albicans. Microbiology 151: 1061– 1071.

62. Sharkey, L. L.,, M. D. McNemar,, S. M. Saporito-Irwin,, P. S. Sypherd, and, W. A. Fonzi. 1999. HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1. J. Bacteriol. 181: 5273– 5279.

63. Sheppard, D. C.,, M. R. Yeaman,, W. H. Welch,, Q. T. Phan,, Y. Fu,, A. S. Ibrahim,, S. G. Filler,, M. Zhang,, A. J. Waring, and, J. E. Edwards, Jr. 2004. Functional and structural diversity in the Als protein family of Candida albicans. J. Biol. Chem. 279: 30840– 30849.

64. Singleton, D. R., and, K. C. Hazen. 2004. Differential surface localization and temperature-dependent expression of the Candida albicans CSH1 protein. Microbiology 150: 285– 292.

65. Singleton, D. R.,, J. Masuoka, and, K. C. Hazen. 2001. Cloning and analysis of a Candida albicans gene that affects cell surface hydrophobicity. J. Bacteriol. 183: 3582– 3588.

66. Spellberg, B. J.,, A. S. Ibrahim,, V. Avenissian,, S. G. Filler,, C. L. Myers,, Y. Fu, and, J. E. Edwards, Jr. 2005. The anti- Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect. Immun. 73: 6191– 6193.

67. Staab, J. F.,, Y. S. Bahn,, C. H. Tai,, P. F. Cook, and, P. Sundstrom. 2004. Expression of transglutaminase substrate activity on Candida albicans germ tubes through a coiled, disulfide-bonded N-terminal domain of Hwp1 requires C-terminal glycosylphosphatidylinositol modification. J. Biol. Chem. 279: 40737– 40747.

68. 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: 1535– 1538.

69. Staab, J. F.,, C. A. Ferrer, and, P. Sundstrom. 1996. Developmental expression of a tandemly repeated, proline-and glutamine- rich amino acid motif on hyphal surfaces on Candida albicans. J. Biol. Chem. 271: 6298– 6305.

70. Staab, J. F., and, P. Sundstrom. 1998. Genetic organization and sequence analysis of the hypha-specific cell wall protein gene HWP1 of Candida albicans. Yeast 14: 681– 686.

71. Sundstrom, P.,, E. Balish, and, C. M. Allen. 2002. Essential role of the Candida albicans transglutaminase substrate, hyphal wall protein 1, in lethal oroesophageal candidiasis in immunodeficient mice. J. Infect. Dis. 185: 521– 530.

72. 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: 3281– 3283.

73. Thau, N.,, M. Monod,, B. Crestani,, C. Rolland,, G. Tronchin,, J. P. Latge, and, S. Paris. 1994. Rodletless mutants of Aspergillus fumigatus. Infect. Immun. 62: 4380– 4388.

74. Tsuchimori, N.,, L. L. Sharkey,, W. A. Fonzi,, S. W. French,, J. E. Edwards, Jr., and, S. G. Filler. 2000. Reduced virulence of HWP1-deficient mutants of Candida albicans and their interactions with host cells. Infect. Immun. 68: 1997– 2002.

75. Wasylnka, J. A., and, M. M. Moore. 2000. Adhesion of Aspergillus species to extracellular matrix proteins: evidence for involvement of negatively charged carbohydrates on the conidial surface. Infect. Immun. 68: 3377– 3384.

76. Willis, A. M.,, W. A. Coulter,, C. R. Fulton,, J. R. Hayes,, P. M. Bell, and, P. J. Lamey. 1999. Oral candidal carriage and infection in insulin-treated diabetic patients. Diabet. Med. 16: 675– 679.

77. Wojciechowicz, D.,, C. F. Lu,, J. Kurjan, and, P. N. Lipke. 1993. Cell surface anchorage and ligand-binding domains of the Saccharomyces cerevisiae cell adhesion protein α-agglutinin, a member of the immunoglobulin superfamily. Mol. Cell. Biol. 13: 2554– 2563.

78. Zhang, N.,, A. L. Harrex,, B. R. Holland,, L. E. Fenton,, R. D. Cannon, and, J. Schmid. 2003. Sixty alleles of the ALS7 open reading frame in Candida albicans: ALS7 is a hypermutable contingency locus. Genome Res. 13: 2005– 2017.

79. Zhao, X.,, S. H. Oh,, G. Cheng,, C. B. Green,, J. A. Nuessen,, K. Yeater,, R. P. Leng,, A. J. Brown, and, L. L. Hoyer. 2004. ALS3 and ALS8 represent a single locus that encodes a Candida albicans adhesin; functional comparisons between Als3p and Als1p. Microbiology 150: 2415– 2428.

80. Zhao, X.,, S. H. Oh,, K. M. Yeater, and, L. L. Hoyer. 2005. Analysis of the Candida albicans Als2p and Als4p adhesins suggests the potential for compensatory function within the Als family. Microbiology 151: 1619– 1630.

81. Zhao, X.,, C. Pujol,, D. R. Soll, and, L. L. Hoyer. 2003. Allelic variation in the contiguous loci encoding Candida albicans ALS5, ALS1 and ALS9. Microbiology 149: 2947– 2960.