Home LiteratureArticle Details
PMID: 14665461 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

EAP1, a Candida albicans gene involved in binding human epithelial cells.

Eukaryotic cell ·Vol. 2 ·No. 6 ·2003-12-00 ·Pages 1266-73

Li F, Palecek SP

Abstract

Candida albicans adhesion to host tissues contributes to its virulence and adhesion to medical devices permits biofilm formation, but we know relatively little about the molecular mechanisms governing C. albicans adhesion to materials or mammalian cells. Saccharomyces cerevisiae provides an attractive model system for studying adhesion in yeast because of its well-characterized genetics and gene expression systems and the conservation of signal transduction pathways among the yeasts. In this study, we used a parallel plate flow chamber to screen and characterize attachment of a flo8Delta S. cerevisiae strain expressing a C. albicans genomic library to a polystyrene surface. The gene EAP1 was isolated as a putative cell wall adhesin. Sequence analysis of EAP1 shows that it contains a signal peptide, a glycosylphosphatidylinositol anchor site, and possesses homology to many other yeast genes encoding cell wall proteins. In addition to increasing adhesion to polystyrene, heterologous expression of EAP1 in S. cerevisiae and autonomous expression of EAP1 in a C. albicans efg1 homozygous null mutant significantly enhanced attachment to HEK293 kidney epithelial cells. EAP1 expression also restored invasive growth to haploid flo8Delta and flo11Delta strains as well as filamentous growth to diploid flo8/flo8 and flo11/flo11 strains. Transcription of EAP1 in C. albicans is regulated by the transcription factor Efg1p, suggesting that EAP1 expression is activated by the cyclic AMP-dependent protein kinase pathway.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Candida albicans/genetics,isolation & purification,metabolism Cell Adhesion Cell Line Conserved Sequence Epithelial Cells/metabolism Fungal Proteins/chemistry Gene Expression Regulation, Fungal Genes, Fungal Humans Kidney/cytology Molecular Sequence Data Polystyrenes/metabolism Saccharomyces cerevisiae/genetics,isolation & purification,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Sequence Homology, Amino Acid Signal Transduction Transcription Factors/genetics,metabolism
Chemicals
Fungal Proteins Polystyrenes Saccharomyces cerevisiae Proteins Transcription Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Li Fang
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Palecek Sean P
References (63)
63 references, click to expand
  1. Regulation of G2/M progression by the STE mitogen-activated protein kinase pathway in budding yeast filamentous growth.
    Mol Biol Cell. 1999 Oct;10(10):3301-16 PMID: 10512868
  2. Adhesion in Candida spp.
    Cell Microbiol. 2002 Aug;4(8):461-9 PMID: 12174081
  3. A recyclable Candida albicans URA3 cassette for PCR product-directed gene disruptions.
    Yeast. 2000 Jan 15;16(1):65-70 PMID: 10620776
  4. Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans.
    Mol Microbiol. 2000 Jan;35(2):386-96 PMID: 10652099
  5. Pseudohyphal development of Saccharomyces cerevisiae.
    Contrib Microbiol. 2000;5:185-200 PMID: 10863673
  6. A Saccharomyces gene family involved in invasive growth, cell-cell adhesion, and mating.
    Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12158-63 PMID: 11027318
  7. Development and use of a parallel-plate flow chamber for studying cellular adhesion to solid surfaces.
    J Biomed Mater Res. 1992 Jun;26(6):725-38 PMID: 1527097
  8. Dominant genetics using a yeast genomic library under the control of a strong inducible promoter.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11589-93 PMID: 1454852
  9. Elements of the yeast pheromone response pathway required for filamentous growth of diploids.
    Science. 1993 Dec 10;262(5140):1741-4 PMID: 8259520
  10. Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth.
    Genes Dev. 1994 Dec 15;8(24):2974-85 PMID: 8001818
  11. Symmetric cell division in pseudohyphae of the yeast Saccharomyces cerevisiae.
    Mol Biol Cell. 1994 Sep;5(9):1003-22 PMID: 7841518
  12. Cloning and expression of a gene encoding an integrin-like protein in Candida albicans.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):357-61 PMID: 8552638
  13. Role of negative regulation in promoter specificity of the homologous transcriptional activators Ace2p and Swi5p.
    Mol Cell Biol. 1996 Apr;16(4):1746-58 PMID: 8657150
  14. EGT2 gene transcription is induced predominantly by Swi5 in early G1.
    Mol Cell Biol. 1996 Jul;16(7):3264-74 PMID: 8668141
  15. Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8419-24 PMID: 8710886
  16. Molecular cloning and analysis of the dominant flocculation gene FLO8 from Saccharomyces cerevisiae.
    Mol Gen Genet. 1996 Jul 26;251(6):707-15 PMID: 8757402
  17. Saccharomyces cerevisiae S288C has a mutation in FLO8, a gene required for filamentous growth.
    Genetics. 1996 Nov;144(3):967-78 PMID: 8913742
  18. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites.
    Protein Eng. 1997 Jan;10(1):1-6 PMID: 9051728
  19. Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition.
    Mol Biol Cell. 2002 Oct;13(10):3452-65 PMID: 12388749
  20. Candida Albicans: a molecular revolution built on lessons from budding yeast.
    Nat Rev Genet. 2002 Dec;3(12):918-30 PMID: 12459722
  21. EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays.
    Mol Microbiol. 2003 Jan;47(1):89-102 PMID: 12492856
  22. The sensing of nutritional status and the relationship to filamentous growth in Saccharomyces cerevisiae.
    FEMS Yeast Res. 2002 Dec;2(4):433-70 PMID: 12702263
  23. Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. I. Evidence for a specific arginine-transporting system.
    Biochim Biophys Acta. 1966 Oct 31;127(2):325-38 PMID: 5964977
  24. Polyoxin D inhibits colloidal gold-wheat germ agglutinin labelling of chitin in dimorphic forms of Candida albicans.
    J Gen Microbiol. 1986 Jun;132(6):1441-51 PMID: 3543207
  25. Candida species: emerging hospital bloodstream pathogens.
    Infect Control Hosp Epidemiol. 1991 Sep;12(9):523-4 PMID: 1940274
  26. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS.
    Cell. 1992 Mar 20;68(6):1077-90 PMID: 1547504
  27. Improved method for high efficiency transformation of intact yeast cells.
    Nucleic Acids Res. 1992 Mar 25;20(6):1425 PMID: 1561104
  28. Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi.
    EMBO J. 1997 Apr 15;16(8):1982-91 PMID: 9155024
  29. Control of filament formation in Candida albicans by the transcriptional repressor TUP1.
    Science. 1997 Jul 4;277(5322):105-9 PMID: 9204892
  30. Nonfilamentous C. albicans mutants are avirulent.
    Cell. 1997 Sep 5;90(5):939-49 PMID: 9298905
  31. Expression, cloning, and characterization of a Candida albicans gene, ALA1, that confers adherence properties upon Saccharomyces cerevisiae for extracellular matrix proteins.
    Infect Immun. 1997 Dec;65(12):5289-94 PMID: 9393828
  32. The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae.
    Mol Biol Cell. 1998 Jan;9(1):161-71 PMID: 9436998
  33. Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1.
    Science. 1998 Feb 27;279(5355):1355-8 PMID: 9478896
  34. Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces adherence to endothelial and epithelial cells.
    Infect Immun. 1998 Apr;66(4):1783-6 PMID: 9529114
  35. Cell wall and secreted proteins of Candida albicans: identification, function, and expression.
    Microbiol Mol Biol Rev. 1998 Mar;62(1):130-80 PMID: 9529890
  36. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
    Yeast. 1998 Jul;14(10):953-61 PMID: 9717241
  37. Amino acid sequence requirement for efficient incorporation of glycosylphosphatidylinositol-associated proteins into the cell wall of Saccharomyces cerevisiae.
    J Biol Chem. 1998 Oct 9;273(41):26946-53 PMID: 9756943
  38. Ace2p, a regulator of CTS1 (chitinase) expression, affects pseudohyphal production in Saccharomyces cerevisiae.
    Curr Genet. 1998 Sep;34(3):183-91 PMID: 9745020
  39. MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene.
    EMBO J. 1999 Mar 1;18(5):1257-69 PMID: 10064592
  40. Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1.
    Science. 1999 Mar 5;283(5407):1535-8 PMID: 10066176
  41. Dimorphism and virulence in Candida albicans.
    Curr Opin Microbiol. 1998 Dec;1(6):687-92 PMID: 10066539
  42. Amino acid residues in the omega-minus region participate in cellular localization of yeast glycosylphosphatidylinositol-attached proteins.
    J Bacteriol. 1999 Jul;181(13):3886-9 PMID: 10383953
  43. An adhesin of the yeast pathogen Candida glabrata mediating adherence to human epithelial cells.
    Science. 1999 Jul 23;285(5427):578-82 PMID: 10417386
  44. Regulatory networks controlling Candida albicans morphogenesis.
    Trends Microbiol. 1999 Aug;7(8):333-8 PMID: 10431207
  45. Adhesins in Candida albicans.
    Curr Opin Microbiol. 1999 Aug;2(4):353-7 PMID: 10458989
  46. HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1.
    J Bacteriol. 1999 Sep;181(17):5273-9 PMID: 10464197
  47. Genetic analysis reveals that FLO11 upregulation and cell polarization independently regulate invasive growth in Saccharomyces cerevisiae.
    Genetics. 2000 Nov;156(3):1005-23 PMID: 11063681
  48. Control of pseudohyphae formation in Saccharomyces cerevisiae.
    FEMS Microbiol Rev. 2001 Jan;25(1):107-23 PMID: 11152942
  49. Fungal morphogenesis and virulence.
    Med Mycol. 2000;38 Suppl 1:79-86 PMID: 11204167
  50. Candida albicans: adherence, signaling and virulence.
    Med Mycol. 2000;38 Suppl 1:125-37 PMID: 11204138
  51. Bakers' yeast, a model for fungal biofilm formation.
    Science. 2001 Feb 2;291(5505):878-81 PMID: 11157168
  52. Inhibition of hydrophobic protein-mediated Candida albicans attachment to endothelial cells during physiologic shear flow.
    Infect Immun. 2001 May;69(5):2815-20 PMID: 11292693
  53. Development of Streptococcus thermophilus lacZ as a reporter gene for Candida albicans.
    Microbiology. 2001 May;147(Pt 5):1189-95 PMID: 11320122
  54. Cloning and analysis of a Candida albicans gene that affects cell surface hydrophobicity.
    J Bacteriol. 2001 Jun;183(12):3582-8 PMID: 11371521
  55. Efg1, a morphogenetic regulator in Candida albicans, is a sequence-specific DNA binding protein.
    J Bacteriol. 2001 Jul;183(13):4090-3 PMID: 11395474
  56. Candida albicans Int1p interacts with the septin ring in yeast and hyphal cells.
    Mol Biol Cell. 2001 Nov;12(11):3538-49 PMID: 11694587
  57. Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans.
    Mol Biol Cell. 2001 Nov;12(11):3631-43 PMID: 11694594
  58. Transcriptional control of dimorphism in Candida albicans.
    Curr Opin Microbiol. 2001 Dec;4(6):728-35 PMID: 11731326
  59. Ura-status-dependent adhesion of Candida albicans mutants.
    FEMS Microbiol Lett. 2001 Nov 13;204(2):323-8 PMID: 11731143
  60. In vitro reconstructed human epithelia reveal contributions of Candida albicans EFG1 and CPH1 to adhesion and invasion.
    Microbiology. 2002 Feb;148(Pt 2):497-506 PMID: 11832513
  61. Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1 filamentation pathway.
    Mol Microbiol. 2002 Apr;44(1):61-72 PMID: 11967069
  62. Depression of Saccharomyces cerevisiae invasive growth on non-glucose carbon sources requires the Snf1 kinase.
    Mol Microbiol. 2002 Jul;45(2):453-69 PMID: 12123456
  63. Analysis of the genes activated by the FLO8 gene in Saccharomyces cerevisiae.
    Curr Genet. 1999 Nov;36(5):256-61 PMID: 10591965
Article Info
Journal
Eukaryotic cell
Abbr.
Eukaryot Cell
ISSN
1535-9778
Published
2003-12-00
Pages
1266-73
Language
English
Region
United States
NLM ID
101130731
PMCID
PMC326646
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]