1887

Abstract

The ability of to act as an opportunistic fungal pathogen is linked to its ability to switch among different morphological forms. This conversion is an important feature of and is correlated with its pathogenesis. Many conserved positive and negative transcription factors regulate morphogenetic transition of . Here, we show the results of functional analysis of , which is an orthologue of the gene. We have cloned which has an ability to complement the . Δ mutant strain growth defect. Interestingly, although disruption of the gene did not affect cell growth in solid and liquid iron-limited conditions, the cell surface ferric reductase activity was significantly decreased. Importantly, deletion of in led to growth of a smooth colony with no peripheral hyphae. Moreover, virulence of an Δ/Δ mutant was markedly attenuated in a mouse model. Our results suggest that Aft2p represents a novel activator and that it functions in ferric reductase activity, morphogenesis and virulence in .

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.037978-0
2010-10-01
2020-07-07
Loading full text...

Full text loading...

/deliver/fulltext/micro/156/10/2912.html?itemId=/content/journal/micro/10.1099/mic.0.037978-0&mimeType=html&fmt=ahah

References

  1. Almeida R. S., Wilson D., Hube B.. 2009; Candida albicans iron acquisition within the host. FEMS Yeast Res9:1000–1012
    [Google Scholar]
  2. Baek Y. U., Li M., Davis D. A.. 2008; Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors. Eukaryot Cell7:1168–1179
    [Google Scholar]
  3. Banerjee M., Thompson D. S., Lazzell A., Carlisle P. L., Pierce C., Monteagudo C., López-Ribot J. L., Kadosh D.. 2008; UME6, a novel filament-specific regulator of Candida albicans hyphal extension and virulence. Mol Biol Cell19:1354–1365
    [Google Scholar]
  4. Barelle C. J., Priest C. L., MacCallum D. M., Gow N. A. R., Odds F. C., Brown A. J. P.. 2006; Niche-specific regulation of central metabolic pathways in a fungal pathogen. Cell Microbiol8:961–971
    [Google Scholar]
  5. Berman J.. 2006; Morphogenesis and cell cycle progression in Candida albicans. Curr Opin Microbiol9:595–601
    [Google Scholar]
  6. Biswas S., Van D. P., Datta A.. 2007; Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol Mol Biol Rev71:348–376
    [Google Scholar]
  7. Blaiseau P. L., Lesuisse E., Camadro J. M.. 2001; Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p, intracellular iron use and resistance to oxidative stress in yeast. J Biol Chem276:34221–34226
    [Google Scholar]
  8. Byers B. R., Arceneaux J. E. L.. 1998; Microbial iron transport: iron acquisition by pathogenic microorganisms. Met Ions Biol Syst35:37–66
    [Google Scholar]
  9. Cao F., Lane S., Raniga P. P., Lu Y., Zhou Z., Ramon K., Chen J., Liu H.. 2006; The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans. Mol Biol Cell17:295–307
    [Google Scholar]
  10. Carlisle P. L., Banerjee M., Lazzell A., Monteagudo C., Lopez-Ribot J. L., Kadosh D.. 2009; Expression levels of a filament-specific transcriptional regulator are sufficient to determine Candida albicans morphology and virulence. Proc Natl Acad Sci U S A106:599–604
    [Google Scholar]
  11. Casas C., Aldea M., Espinet C., Gallego C., Gil R., Herrero E.. 1997; The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae. Yeast13:621–643
    [Google Scholar]
  12. Courel M., Lallet S., Camadro J. M., Blaiseau P. L.. 2005; Direct activation of genes involved in intracellular iron use by the yeast iron-responsive transcription factor Aft2 without its paralog Aft1. Mol Cell Biol25:6760–6771
    [Google Scholar]
  13. Davis D., Edwards J. E. Jr, Mitchell A. P., Ibrahim A. S.. 2000a; Candida albicans RIM101 pH response pathway is required for host-pathogen interactions. Infect Immun68:5953–5959
    [Google Scholar]
  14. Davis D., Wilson R. B., Mitchell A. P.. 2000b; RIM101-dependent and-independent pathways govern pH responses in Candida albicans. Mol Cell Biol20:971–978
    [Google Scholar]
  15. Doedt T., Krishnamurthy S., Bockmühl D. P. B., Tebarth B., Stempel C., Russel C. L., Brown A. J. P., Ernst J. F.. 2004; APSES proteins regulate morphogenesis and metabolism in Candida albicans. Mol Biol Cell15:3167–3180
    [Google Scholar]
  16. Homann O. R., Dea J., Noble S. M., Johnson A. D.. 2009; A phenotypic profile of the Candida albicans regulatory network. PLoS Genet5:e1000783
    [Google Scholar]
  17. Klepser M. E.. 2006; Candida resistance and its clinical relevance. Pharmacotherapy26:68S–75S
    [Google Scholar]
  18. Knight S. A., Vilaire G., Lesuisse E., Dancis A.. 2005; Iron acquisition from transferrin by Candida albicans depends on the reductive pathway. Infect Immun73:5482–5492
    [Google Scholar]
  19. 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 Microbiol53:1451–1469
    [Google Scholar]
  20. Liang Y., Gui L., Wei D.-S., Zheng W., Xing L.-J., Li M.-C.. 2009; Candida albicans ferric reductase FRP1 is regulated by direct interaction with Rim101p transcription factor. FEMS Yeast Res9:270–277
    [Google Scholar]
  21. Liu H., Köhler J., Fink G. R.. 1994; Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science266:1723–1726
    [Google Scholar]
  22. Lo H. J., Köhler J. R., DiDomenico B., Loebenberg D., Cacciapuoti A., Fink G. R.. 1997; Nonfilamentous C. albicans mutants are avirulent. Cell90:939–949
    [Google Scholar]
  23. Mitchell P. J., Tjian R.. 1989; Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science245:371–378
    [Google Scholar]
  24. Murad A. M. A., d'Enfert C., Gaillardin C., Tournu L., Tekaia F., Talibi D., Marechal D., Marchais V., Cottin J., Brown A. J. P.. 2001; Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1. Mol Microbiol42:981–993
    [Google Scholar]
  25. Philpott C. C., Protchenko O.. 2008; Response to iron deprivation in Saccharomyces cerevisiae. Eukaryot Cell7:20–27
    [Google Scholar]
  26. Ramanan N., Wang Y.. 2000; A high-affinity iron permease essential for Candida albicans virulence. Science288:1062–1064
    [Google Scholar]
  27. Rutherford J. C., Jaron S., Ray E., Brown P. O., Winge D. R.. 2001; A second iron-regulatory system in yeast independent of Aft1p. Proc Natl Acad Sci U S A98:14322–14327
    [Google Scholar]
  28. Rutherford J. C., Jaron S., Winge D. R.. 2003; Aft1p and Aft2p mediate iron-responsive gene expression in yeast through related promoter elements. J Biol Chem278:27636–27643
    [Google Scholar]
  29. Thomas B. J., Rothstein R.. 1989; Elevated recombination rates in transcriptionally active DNA. Cell56:619–630
    [Google Scholar]
  30. Wilson R. B., Davis D., Mitchell A. P.. 1999; Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol181:1868–1874
    [Google Scholar]
  31. Yamaguchi-Iwai Y., Dancis A., Klausner R. D.. 1995; AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae. EMBO J14:1231–1239
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.037978-0
Loading
/content/journal/micro/10.1099/mic.0.037978-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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