Candida glabrata EPA7

From CFGparadigms

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
'''Fungal adhesins with lectin properties'''<br>
'''Fungal adhesins with lectin properties'''<br>
-
Cell adhesion proteins on fungal cell surfaces mediate interactions both with other cells of the same type and with the external environment (Douglas, et al. 2007, Dranginis, et al. 2007). These interactions impact critical processes including mating, pathogenesis, and biofilm formation. Fungal adhesins are typically GPI-anchored proteins that have been covalently liked to the cell wall, such that their N-terminal ligand binding domains extend from the cell surface. They frequently occur as families of related proteins (Tronchin, et al. 2008). Members of two such groups, the flocculation/agglutination genes of the model yeast ''Saccharomyces cerevisiae'' (Kobayashi, et al. 1998) and the related EPA genes (Kaur, et al. 2005) of the pathogenic fungus Candida glabrata, are lectins. Several of the 23 identified EPA genes have been functionally shown to mediate binding of C. glabrata to host cells (Castano, et al. 2005, Domergue, et al. 2005), an essential step in infection and virulence. Defining the specificity of these proteins and their biological roles will elucidate the interactions between host and pathogen, and potentially indicate ways in which to inhibit them for the benefit of the host.
+
Cell adhesion proteins on fungal cell surfaces mediate interactions both with other cells of the same type and with the external environment<ref>Douglas, L.M., Li, L., Yang, Y. and Dranginis, A.M. 2007. Expression and characterization of the flocculin Flo11/Muc1, a Saccharomyces cerevisiae mannoprotein with homotypic properties of adhesion. Eukaryot Cell, 6, 2214-2221.</ref><ref>Dranginis, A.M., Rauceo, J.M., Coronado, J.E. and Lipke, P.N. 2007. A biochemical guide to yeast adhesins: glycoproteins for social and antisocial occasions. Microbiol Mol Biol Rev, 71, 282-294.</ref>. These interactions impact critical processes including mating, pathogenesis, and biofilm formation. Fungal adhesins are typically GPI-anchored proteins that have been covalently liked to the cell wall, such that their N-terminal ligand binding domains extend from the cell surface. They frequently occur as families of related proteins<ref>Tronchin, G., Pihet, M., Lopes-Bezerra, L.M. and Bouchara, J.P. 2008. Adherence mechanisms in human pathogenic fungi. Med Mycol, 46, 749-772. </ref>. Members of two such groups, the flocculation/agglutination genes of the model yeast ''Saccharomyces cerevisiae''<ref>Kobayashi, O., Hayashi, N., Kuroki, R. and Sone, H. 1998. Region of FLO1 proteins responsible for sugar recognition. J Bacteriol, 180, 6503-6510.</ref> and the related EPA genes<ref>Kaur, R., Domergue, R., Zupancic, M.L. and Cormack, B.P. 2005. A yeast by any other name: Candida glabrata and its interaction with the host. Curr Opin Microbiol, 8, 378-384.</ref> of the pathogenic fungus ''Candida glabrata'', are lectins. Several of the 23 identified EPA genes have been functionally shown to mediate binding of ''C. glabrata'' to host cells<ref name="Castano 2005">Castano, I., Pan, S.J., Zupancic, M., Hennequin, C., Dujon, B. and Cormack, B.P. 2005. Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata. Mol Microbiol, 55, 1246-1258.</ref><ref>Domergue, R., Castano, I., de las Penas, A., Zupancic, M., Lockatell, V., Hebel, J.R. et al. 2005. Nicotinic acid limiation regulates silencing of Candida albicans adhesins during UTI. Science, 308, 866-870.</ref>, an essential step in infection and virulence. Defining the specificity of these proteins and their biological roles will elucidate the interactions between host and pathogen, and potentially indicate ways in which to inhibit them for the benefit of the host.
'''''Candida glabrata'' EPA7'''<br>
'''''Candida glabrata'' EPA7'''<br>
-
The EPA family was chosen as a paradigm because of its relevance to a fungal pathogen that affects human health, and which also can be studied in mouse models of infection. EPA7 was chosen to represent this group because it has been demonstrated to function as an adhesin (Castano, et al. 2005) and is one of the EPA proteins that has been studied in the most detail. The N-terminal binding domain of this protein, expressed on the surface of S. cerevisiae, has been analyzed on the CFG glycan array. These studies demonstrated EPA7 binding specificity for β1,3- and β1,4-linked galactosides (Zupancic, et al. 2008; de Groot and Klis, 2008). This work represents a significant step forward in the area of lectin-like fungal adhesins; in general the specificity of these important proteins remains unexplored.
+
The EPA family was chosen as a paradigm because of its relevance to a fungal pathogen that affects human health, and which also can be studied in mouse models of infection. EPA7 was chosen to represent this group because it has been demonstrated to function as an adhesin<ref name="Castano 2005"/> and is one of the EPA proteins that has been studied in the most detail. The N-terminal binding domain of this protein, expressed on the surface of S''. cerevisiae'', has been analyzed on the CFG glycan array. These studies demonstrated EPA7 binding specificity for β1,3- and β1,4-linked galactosides<ref>Zupancic, M.L., Frieman, M., Smith, D., Alvarez, R.A., Cummings, R.D. and Cormack, B.P. 2008. Glycan microarray analysis of Candida glabrata adhesin ligand specificity. Mol Microbiol, 58, 547-559.</ref><ref>de Groot, P.W.J. and Klis, F.M. 2008. The conserved PA14 domain of cell wall-associated fungal adhesins governs their glycan-binding specificity. Mol Microbiol, 68, 535-537. </ref>. This work represents a significant step forward in the area of lectin-like fungal adhesins; in general the specificity of these important proteins remains unexplored.
== CFG Participating Investigators contributing to the understanding of this paradigm ==
== CFG Participating Investigators contributing to the understanding of this paradigm ==

Revision as of 04:49, 10 April 2010

Fungal adhesins with lectin properties
Cell adhesion proteins on fungal cell surfaces mediate interactions both with other cells of the same type and with the external environment[1][2]. These interactions impact critical processes including mating, pathogenesis, and biofilm formation. Fungal adhesins are typically GPI-anchored proteins that have been covalently liked to the cell wall, such that their N-terminal ligand binding domains extend from the cell surface. They frequently occur as families of related proteins[3]. Members of two such groups, the flocculation/agglutination genes of the model yeast Saccharomyces cerevisiae[4] and the related EPA genes[5] of the pathogenic fungus Candida glabrata, are lectins. Several of the 23 identified EPA genes have been functionally shown to mediate binding of C. glabrata to host cells[6][7], an essential step in infection and virulence. Defining the specificity of these proteins and their biological roles will elucidate the interactions between host and pathogen, and potentially indicate ways in which to inhibit them for the benefit of the host.

Candida glabrata EPA7
The EPA family was chosen as a paradigm because of its relevance to a fungal pathogen that affects human health, and which also can be studied in mouse models of infection. EPA7 was chosen to represent this group because it has been demonstrated to function as an adhesin[6] and is one of the EPA proteins that has been studied in the most detail. The N-terminal binding domain of this protein, expressed on the surface of S. cerevisiae, has been analyzed on the CFG glycan array. These studies demonstrated EPA7 binding specificity for β1,3- and β1,4-linked galactosides[8][9]. This work represents a significant step forward in the area of lectin-like fungal adhesins; in general the specificity of these important proteins remains unexplored.

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

  • CFG Participating Investigators (PIs) who have contributed to studies of this paradigmatic protein include: Brendan Cormack, Rick Cummings
  • PIs using CFG resources to study related S. cerevisiae proteins include: Lars-Oliver Essen (several flocculins), Peter Lipke (alpha agglutinin)

Progress toward understanding this GBP paradigm

Carbohydrate ligands


Cellular expression


Structure


Biological roles of GBP-ligand interaction


CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for "EPA7".

Glycan profiling


Glycogene microarray


Knockout mouse lines


Glycan array

The specificity of EPA7 and related proteins was determined through CFG glycan array analysis.

Related GBPs

  • 22 additional EPA family members in C. glabrata
  • Related proteins in S. cerevisiae
  • EPA7-like glycan-binding domain also occurs in predicted proteins of Ashbya gossypii and Kluyveromyces lactis.

References

  1. Douglas, L.M., Li, L., Yang, Y. and Dranginis, A.M. 2007. Expression and characterization of the flocculin Flo11/Muc1, a Saccharomyces cerevisiae mannoprotein with homotypic properties of adhesion. Eukaryot Cell, 6, 2214-2221.
  2. Dranginis, A.M., Rauceo, J.M., Coronado, J.E. and Lipke, P.N. 2007. A biochemical guide to yeast adhesins: glycoproteins for social and antisocial occasions. Microbiol Mol Biol Rev, 71, 282-294.
  3. Tronchin, G., Pihet, M., Lopes-Bezerra, L.M. and Bouchara, J.P. 2008. Adherence mechanisms in human pathogenic fungi. Med Mycol, 46, 749-772.
  4. Kobayashi, O., Hayashi, N., Kuroki, R. and Sone, H. 1998. Region of FLO1 proteins responsible for sugar recognition. J Bacteriol, 180, 6503-6510.
  5. Kaur, R., Domergue, R., Zupancic, M.L. and Cormack, B.P. 2005. A yeast by any other name: Candida glabrata and its interaction with the host. Curr Opin Microbiol, 8, 378-384.
  6. 6.0 6.1 Castano, I., Pan, S.J., Zupancic, M., Hennequin, C., Dujon, B. and Cormack, B.P. 2005. Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata. Mol Microbiol, 55, 1246-1258.
  7. Domergue, R., Castano, I., de las Penas, A., Zupancic, M., Lockatell, V., Hebel, J.R. et al. 2005. Nicotinic acid limiation regulates silencing of Candida albicans adhesins during UTI. Science, 308, 866-870.
  8. Zupancic, M.L., Frieman, M., Smith, D., Alvarez, R.A., Cummings, R.D. and Cormack, B.P. 2008. Glycan microarray analysis of Candida glabrata adhesin ligand specificity. Mol Microbiol, 58, 547-559.
  9. de Groot, P.W.J. and Klis, F.M. 2008. The conserved PA14 domain of cell wall-associated fungal adhesins governs their glycan-binding specificity. Mol Microbiol, 68, 535-537.

Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page: Richard Cummings, Tamara Doering

Personal tools