1887

Abstract

The opportunistic fungal pathogen has developed various ways to overcome iron restriction in a mammalian host. Using different surface proteins, among them membrane- and wall-localized glycosylphosphatidylinositol (GPI) proteins, it can exploit iron from host haemoglobin, ferritin and transferrin. Culturing in rich medium supplemented with the ferrous iron chelator bathophenanthroline disulfonic acid or in the minimal medium yeast nitrogen base resulted in a strong decrease of the iron content of the cells. MS analysis of the changes in the wall proteome of upon iron restriction showed a strong increase in the levels of the GPI-modified adhesin Als3, which also serves as a ferritin receptor, and of the GPI-modified CFEM (common in fungal extracellular membranes) domain-containing proteins Csa1, Pga7, Pga10, and Rbt5. The wall levels of the GPI-modified proteins Hyr1, the adhesin Als4 and the copper- and zinc-containing superoxide dismutase Sod4 also strongly increased, whereas the levels of Tos1 (a non-GPI protein) and the GPI-modified adhesin Als2 strongly decreased. Strikingly, peptides derived from the CFEM domain of the haem-binding proteins Csa1, Pga10 and Rbt5 were capable of forming iron adduct ions during MS analysis, consistent with a key role of this domain in haem binding.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.065599-0
2013-08-01
2021-08-03
Loading full text...

Full text loading...

/deliver/fulltext/micro/159/8/1673.html?itemId=/content/journal/micro/10.1099/mic.0.065599-0&mimeType=html&fmt=ahah

References

  1. Almeida R. S., Brunke S., Albrecht A., Thewes S., Laue M., Edwards J. E., Filler S. G., Hube B. ( 2008). The hyphal-associated adhesin and invasin Als3 of Candida albicans mediates iron acquisition from host ferritin. PLoS Pathog 4:e1000217 [View Article]
    [Google Scholar]
  2. Almeida R. S., Wilson D., Hube B. ( 2009). Candida albicans iron acquisition within the host. FEMS Yeast Res 9:1000–1012 [View Article]
    [Google Scholar]
  3. Ardon O., Bussey H., Philpott C., Ward D. M., Davis-Kaplan S., Verroneau S., Jiang B., Kaplan J. ( 2001). Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae . J Biol Chem 276:43049–43055 [View Article]
    [Google Scholar]
  4. Bailey D. A., Feldmann P. J., Bovey M., Gow N. A., Brown A. J. ( 1996). The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins. J Bacteriol 178:5353–5360
    [Google Scholar]
  5. Barr I., Smith A. T., Senturia R., Chen Y., Scheidemantle B. D., Burstyn J. N., Guo F. ( 2010). DiGeorge critical region 8 (DGCR8) is a double-cysteine-ligated heme protein. J Biol Chem 286:16716–16725 [CrossRef]
    [Google Scholar]
  6. Braun V., Hantke K. ( 2011). Recent insights into iron import by bacteria. Curr Opin Chem Biol 15:328–334 [View Article]
    [Google Scholar]
  7. Brena S., Cabezas-Olcoz J., Moragues M. D., Fernandez de Larrinoa I., Dominguez A., Quindos G., Ponton J. ( 2011). Fungicidal monoclonal antibody C7 interferes with iron acquisition in Candida albicans . Antimicrob Agents Chemother 55:3156–3163 [View Article]
    [Google Scholar]
  8. Bullen J. J., Rogers H. J., Spalding P. B., Ward C. G. ( 2006). Natural resistance, iron and infection: a challenge for clinical medicine. J Med Microbiol 55:251–258 [View Article]
    [Google Scholar]
  9. Chen C., Pande K., French S. D., Tuch B. B., Noble S. M. ( 2011). An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis. Cell Host Microbe 10:118–135 [View Article]
    [Google Scholar]
  10. Citiulo F., Jacobsen I. D., Miramon P., Schild L., Brunke S., Zipfel P., Brock M., Hube B., Wilson D. ( 2012). Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLoS Pathog 8:e1002777 [View Article]
    [Google Scholar]
  11. De Luca N. G., Wood P. M. ( 2000). Iron uptake by fungi: contrasted mechanisms with internal or external reduction. Adv Microb Physiol 43:39–74 [View Article]
    [Google Scholar]
  12. Ding C., Vidanes G. M., Maguire S. L., Guida A., Synnott J. M., Andes D. R., Butler G. ( 2011). Conserved and divergent roles of Bcr1 and CFEM proteins in Candida parapsilosis and Candida albicans . PLoS ONE 6:e28151 [View Article]
    [Google Scholar]
  13. Eide D. J., Clark S., Nair T. M., Gehl M., Gribskov M., Guerinot M. L., Harper J. F. ( 2005). Characterization of the yeast ionome: a genome-wide analysis of nutrient mineral and trace element homeostasis in Saccharomyces cerevisiae . Genome Biol 6, R77 [View Article]
    [Google Scholar]
  14. Foster L. A. ( 2002). Utilization and cell-surface binding of hemin by Histoplasma capsulatum . Can J Microbiol 48:437–442 [View Article]
    [Google Scholar]
  15. Gillum A. M., Tsay E. Y., Kirsch D. R. ( 1984). Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198:179–182 [View Article]
    [Google Scholar]
  16. Gow N. A., Gooday G. W. ( 1982). Vacuolation, branch production and linear growth of germ tubes in Candida albicans . J Gen Microbiol 128:2195–2198
    [Google Scholar]
  17. Grigg J. C., Ukpabi G., Gaudin C. F., Murphy M. E. ( 2010). Structural biology of heme binding in the Staphylococcus aureus Isd system. J Inorg Biochem 104:341–348 [View Article]
    [Google Scholar]
  18. Hameed S., Prasad T., Banerjee D., Chandra A., Mukhopadhyay C. K., Goswami S. K., Lattif A. A., Chandra J., Mukherjee P. K. & other authors ( 2008). Iron deprivation induces EFG1-mediated hyphal development in Candida albicans without affecting biofilm formation. FEMS Yeast Res 8:744–755 [View Article]
    [Google Scholar]
  19. Han Y. ( 2005). Utilization of ferroproteins by Candida albicans during candidastasis by apotransferrin. Arch Pharm Res 28:963–969 [View Article]
    [Google Scholar]
  20. Heilmann C. J., Sorgo A. G., Siliakus A. R., Dekker H. L., Brul S., de Koster C. G., de Koning L. J., Klis F. M. ( 2011). Hyphal induction in the human fungal pathogen Candida albicans reveals a characteristic wall protein profile. Microbiology 157:2297–2307 [View Article]
    [Google Scholar]
  21. Heilmann C. J., Sorgo A. G., Mohammadi S., Sosinska G. J., de Koster C. G., Brul S., de Koning L. J., Klis F. M. ( 2013). Surface stress induces a conserved cell wall stress response in the pathogenic fungus Candida albicans . Eukaryot Cell 12:254–264 [View Article]
    [Google Scholar]
  22. Inglis D. O., Arnaud M. B., Binkley J., Shah P., Skrzypek M. S., Wymore F., Binkley G., Miyasato S. R., Simison M., Sherlock G. ( 2012). The Candida genome database incorporates multiple Candida species: multispecies search and analysis tools with curated gene and protein information for Candida albicans and Candida glabrata . Nucleic Acids Res 40:D1D667–D674 [View Article]
    [Google Scholar]
  23. Johnson K. A., Shira B. A., Anderson J. L., Amster I. J. ( 2001). Chemical and on-line electrochemical reduction of metalloproteins with high-resolution electrospray ionization mass spectrometry detection. Anal Chem 15:803–808 [View Article]
    [Google Scholar]
  24. Knight S. A., Vilaire G., Lesuisse E., Dancis A. ( 2005). Iron acquisition from transferrin by Candida albicans depends on the reductive pathway. Infect Immun 73:5482–5492 [View Article]
    [Google Scholar]
  25. Kosman D. J. ( 2003). Molecular mechanisms of iron uptake in fungi. Mol Microbiol 47:1185–1197 [View Article]
    [Google Scholar]
  26. Kulkarni R. D., Kelkar H. S., Dean R. A. ( 2003). An eight-cysteine-containing CFEM domain unique to a group of fungal membrane proteins. Trends Biochem Sci 28:118–121 [View Article]
    [Google Scholar]
  27. Lan C. Y., Rodarte G., Murillo L. A., Jones T., Davis R. W., Dungan J., Newport G., Agabian N. ( 2004). Regulatory networks affected by iron availability in Candida albicans . Mol Microbiol 53:1451–1469 [View Article]
    [Google Scholar]
  28. Lee R. E., Liu T. T., Barker K. S., Rogers P. D. ( 2005). Genome-wide expression profiling of the response to ciclopirox olamine in Candida albicans . J Antimicrob Chemother 55:655–662 [View Article]
    [Google Scholar]
  29. Martchenko M., Alarco A. M., Harcus D., Whiteway M. ( 2004). Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene. Mol Biol Cell 15:456–467 [View Article]
    [Google Scholar]
  30. Mazmanian S. K., Skaar E. P., Gaspar A. H., Humayun M., Gornicki P., Jelenska J., Joachmiak A., Missiakas D. M., Schneewind O. ( 2003). Passage of heme-iron across the envelope of Staphylococcus aureus . Science 299:906–909 [View Article]
    [Google Scholar]
  31. Mrsa V., Ecker M., Strahl-Bolsinger S., Nimtz M., Lehle L., Tanner W. ( 1999). Deletion of new covalently linked cell wall glycoproteins alters the electrophoretic mobility of phosphorylated wall components of Saccharomyces cerevisiae . J Bacteriol 181:3076–3086
    [Google Scholar]
  32. Plaine A., Walker L., Da Costa G., Mora-Montes H. M., McKinnon A., Gow N. A., Gaillardin C., Munro C. A., Richard M. L. ( 2008). Functional analysis of Candida albicans GPI-anchored proteins: roles in cell wall integrity and caspofungin sensitivity. Fungal Genet Biol 45:1404–1414 [View Article]
    [Google Scholar]
  33. Prasad T., Chandra A., Mukhopadhyay C. K., Prasad R. ( 2006). Unexpected link between iron and drug resistance of Candida spp.: iron depletion enhances membrane fluidity and drug diffusion, leading to drug-susceptible cells. Antimicrob Agents Chemother 50:3597–3606 [View Article]
    [Google Scholar]
  34. Protchenko O., Ferea T., Rashford J., Tiedeman J., Brown P. O., Botstein D., Philpott C. C. ( 2001). Three cell wall mannoproteins facilitate the uptake of iron in Saccharomyces cerevisiae . J Biol Chem 276:49244–49250 [View Article]
    [Google Scholar]
  35. Ramanan N., Wang Y. ( 2000). A high-affinity iron permease essential for Candida albicans virulence. Science 288:1062–1064 [View Article]
    [Google Scholar]
  36. Sigle H. C., Thewes S., Niewerth M., Korting H. C., Schafer-Korting M., Hube B. ( 2005). Oxygen accessibility and iron levels are critical factors for the antifungal action of ciclopirox against Candida albicans . J Antimicrob Chemother 55:663–673 [View Article]
    [Google Scholar]
  37. Sorgo A. G., Heilmann C. J., Dekker H. L., Brul S., de Koster C. G., Klis F. M. ( 2010). Mass spectrometric analysis of the secretome of Candida albicans . Yeast 27:661–672 [View Article]
    [Google Scholar]
  38. Sorgo A. G., Heilmann C. J., Dekker H. L., Bekker M., Brul S., de Koster C. G., de Koning L. J., Klis F. M. ( 2011). Effects of fluconazole on the secretome, the wall proteome, and wall integrity of the clinical fungus Candida albicans . Eukaryot Cell 10:1071–1081 [View Article]
    [Google Scholar]
  39. Sosinska G. J., de Groot P. W., Teixeira de Mattos M. J., Dekker H. L., de Koster C. G., Hellingwerf K. J., Klis F. M. ( 2008). Hypoxic conditions and iron restriction affect the cell-wall proteome of Candida albicans grown under vagina-simulative conditions. Microbiology 154:510–520 [View Article]
    [Google Scholar]
  40. Sosinska G. J., de Koning L. J., de Groot P. W., Manders E. M., Dekker H. L., Hellingwerf K. J., de Koster C. G., Klis F. M. ( 2011). Mass spectrometric quantification of the adaptations in the wall proteome of Candida albicans in response to ambient pH. Microbiology 157:136–146 [View Article]
    [Google Scholar]
  41. Synnott J. M., Guida A., Mulhern-Haughey S., Higgins D. G., Butler G. ( 2010). Regulation of the hypoxic response in Candida albicans . Eukaryot Cell 9:1734–1746 [View Article]
    [Google Scholar]
  42. Tamarit J., Irazusta V., Moreno-Cermeno A., Ros J. ( 2006). Colorimetric assay for the quantitation of iron in yeast. Anal Biochem 351:149–151 [View Article]
    [Google Scholar]
  43. Van Berkel G. J., Kertesz V. ( 2007). Using the electrochemistry of the electrospray ion source. Anal Chem 79:5510–5520 [View Article]
    [Google Scholar]
  44. Ward P. P., Uribe-Luna S., Conneely O. M. ( 2002). Lactoferrin and host defense. Biochem Cell Biol 80:95–102 [View Article]
    [Google Scholar]
  45. Weissman Z., Kornitzer D. ( 2004). A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization. Mol Microbiol 53:1209–1220 [View Article]
    [Google Scholar]
  46. Weissman Z., Shemer R., Kornitzer D. ( 2002). Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron acquisition in Candida albicans . Mol Microbiol 44:1551–1560 [View Article]
    [Google Scholar]
  47. Weissman Z., Shemer R., Conibear E., Kornitzer D. ( 2008). An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans . Mol Microbiol 69:201–217 [View Article]
    [Google Scholar]
  48. Wösten H. A. ( 2001). Hydrophobins: multipurpose proteins. Annu Rev Microbiol 55:625–646 [View Article]
    [Google Scholar]
  49. Yamada-Okabe T., Shimmi O., Doi R., Mizumoto K., Arisawa M., Yamada-Okabe H. ( 1996). Isolation of the mRNA-capping enzyme and ferric-reductase-related genes from Candida albicans . Microbiology 142:2515–2523 [View Article]
    [Google Scholar]
  50. Yin Q. Y., de Groot P. W., Dekker H. L., de Jong L., Klis F. M., de Koster C. G. ( 2005). Comprehensive proteomic analysis of Saccharomyces cerevisiae cell walls: identification of proteins covalently attached via glycosylphosphatidylinositol remnants or mild alkali-sensitive linkages. J Biol Chem 280:20894–20901 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.065599-0
Loading
/content/journal/micro/10.1099/mic.0.065599-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error