1887

Microbiology Society logo

Volume 153, Issue 1

Autophagy in the pathogen Free

Abstract

Autophagy is a major cellular process that facilitates the bulk degradation of eukaryotic macromolecules and organelles, through degradation within the lysosomal/vacuole compartment. This has been demonstrated to influence a diverse array of eukaryotic cell functions including adaptation, differentiation and developmental programmes. For example, in autophagy is required for sporulation and survival of nitrogen starvation. The opportunistic pathogen has the ability to colonize and cause disease within a diverse range of mammalian host sites. The ability to adapt and differentiate within the host is liable to be critical for host colonization and infection. Previous results indicated that the vacuole plays an important role in adaptation to stress, differentiation, and survival within and injury of host cells. In this study the importance of vacuole-mediated degradation through the process of autophagy was investigated. This involved identification and deletion of , a gene required for autophagy. The deletion strain was blocked in autophagy and the closely related cytoplasm to vacuole (cvt) trafficking pathway. This resulted in sensitivity to nitrogen starvation, but no defects in growth rate, vacuole morphology or resistance to other stresses. This indicates that the mutant has specific defects in autophagy/cvt trafficking. Given the importance of autophagy in the development and differentiation of other eukaryotes, it was surprising to find that the Δ mutant was unaffected in either yeast–hypha or chlamydospore differentiation. Furthermore, the Δ mutant survived within and killed a mouse macrophage-like cell line as efficiently as control strains. The data suggest that autophagy plays little or no role in differentiation or during interaction with host cells.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): AMS, α-mannosidase , API, aminopeptidase I , CPY, carboxypeptidase Y , DIC, differential interference contrast and SAP, secreted aspartyl protease
SGM
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2006/001610-0
2007-01-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/1/51.html?itemId=/content/journal/micro/10.1099/mic.0.2006/001610-0&mimeType=html&fmt=ahah

References

  1. Abeliovich H., Klionsky D. J. 2001; Autophagy in yeast: mechanistic insights and physiological function. Microbiol Mol Biol Rev 65:463–479 [CrossRef]
     [Google Scholar]
  2. Barelle C. J., Bohula E. A., Kron S. J., Wessels D., Soll D. R., Schafer A., Brown A. J., Gow N. A. 2003; Asynchronous cell cycle and asymmetric vacuolar inheritance in true hyphae of Candida albicans . Eukaryot Cell 2:398–410 [CrossRef]
     [Google Scholar]
  3. Bensen E. S., Filler S. G., Berman J. 2002; A Forkhead transcription factor is important for true hyphal as well as yeast morphogenesis in Candida albicans . Eukaryotic Cell 1:787–798 [CrossRef]
     [Google Scholar]
  4. Burke D., Dawson D., Stearns T. 2000 Methods in Yeast Genetics: a Cold Spring Harbor Laboratory Course Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
     [Google Scholar]
  5. Crandall M., Edwards J. E. Jr 1987; Segregation of proteinase-negative mutants from heterozygous Candida albicans . J Gen Microbiol 133:2817–2824
     [Google Scholar]
  6. de Repentigny L. Lewandowski D., Jolicoeur P. 2004; Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin Microbiol Rev 17:729–759 [CrossRef]
     [Google Scholar]
  7. Gerami-Nejad M., Berman J., Gale C. A. 2001; Cassettes for PCR-mediated construction of green, yellow, and cyan fluorescent protein fusions in Candida albicans . Yeast 18:859–864 [CrossRef]
     [Google Scholar]
  8. 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]
  9. Gow N. A., Gooday G. W. 1984; A model for the germ tube formation and mycelial growth form of Candida albicans . Sabouraudia 22:137–144 [CrossRef]
     [Google Scholar]
  10. Guthrie C., Fink G. 1991 Guide to Yeast Genetics and Molecular Biology New York: Academic Press;
     [Google Scholar]
  11. Klionsky D. J. 2005; The molecular machinery of autophagy: unanswered questions. J Cell Sci 118:7–18 [CrossRef]
     [Google Scholar]
  12. Klionsky D. J., Cueva R., Yaver D. S. 1992; Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway. J Cell Biol 119:287–299 [CrossRef]
     [Google Scholar]
  13. Kyte J., Doolittle R. F. 1982; A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132 [CrossRef]
     [Google Scholar]
  14. Lang T., Reiche S., Straub M., Bredschneider M., Thumm M. 2000; Autophagy and the cvt pathway both depend on AUT9. J Bacteriol 182:2125–2133 [CrossRef]
     [Google Scholar]
  15. Lorenz M. C., Bender J. A., Fink G. R. 2004; Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3:1076–1087 [CrossRef]
     [Google Scholar]
  16. Maertens J., Vrebos M., Boogaerts M. 2001; Assessing risk factors for systemic fungal infections. Eur J Cancer Care 10:56–62 [CrossRef]
     [Google Scholar]
  17. Mizushima N. 2005; The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ 12 (Suppl. 2):1535–1541 [CrossRef]
     [Google Scholar]
  18. Nair U., Klionsky D. J. 2005; Molecular mechanisms and regulation of specific and nonspecific autophagy pathways in yeast. J Biol Chem 280:41785–41788 [CrossRef]
     [Google Scholar]
  19. Noda T., Kim J., Huang W. P., Baba M., Tokunaga C., Ohsumi Y., Klionsky D. J. 2000; Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. J Cell Biol 148:465–480 [CrossRef]
     [Google Scholar]
  20. Oda M. N., Scott S. V., Hefner-Gravink A., Caffarelli A. D., Klionsky D. J. 1996; Identification of a cytoplasm to vacuole targeting determinant in aminopeptidase I. J Cell Biol 132:999–1010 [CrossRef]
     [Google Scholar]
  21. Palmer G. E., Sturtevant J. E. 2004; Random mutagenesis of an essential Candida albicans gene. Curr Genet 46:343–356 [CrossRef]
     [Google Scholar]
  22. Palmer G. E., Cashmore A., Sturtevant J. 2003; Candida albicans VPS11 is required for vacuole biogenesis and germ tube formation. Eukaryot Cell 2:411–421 [CrossRef]
     [Google Scholar]
  23. Palmer G. E., Johnson K. J., Ghosh S., Sturtevant J. 2004; Mutant alleles of the essential 14-3-3 gene in Candida albicans distinguish between growth and filamentation. Microbiology 150:1911–1924 [CrossRef]
     [Google Scholar]
  24. Palmer G. E., Kelly M. N., Sturtevant J. E. 2005; The Candida albicans vacuole is required for differentiation and efficient macrophage killing. Eukaryot Cell 4:1677–1686 [CrossRef]
     [Google Scholar]
  25. Ramon A. M., Fonzi W. A. 2003; Diverged binding specificity of Rim101p, the Candida albicans ortholog of PacC. Eukaryot Cell 2:718–728 [CrossRef]
     [Google Scholar]
  26. Rocha C. R., Schroppel K., Harcus D., Marcil A., Dignard D., Taylor B. N., Thomas D. Y., Whiteway M., Leberer E. 2001; Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans . Mol Biol Cell 12:3631–3643 [CrossRef]
     [Google Scholar]
  27. Suzuki K., Kamada Y., Ohsumi Y. 2002; Studies of cargo delivery to the vacuole mediated by autophagosomes in Saccharomyces cerevisiae . Dev Cell 3:815–824 [CrossRef]
     [Google Scholar]
  28. Takeshige K., Baba M., Tsuboi S., Noda T., Ohsumi Y. 1992; Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119:301–311 [CrossRef]
     [Google Scholar]
  29. Thumm M., Egner R., Koch B., Schlumpberger M., Straub M., Veenhuis M., Wolf D. H. 1994; Isolation of autophagocytosis mutants of Saccharomyces cerevisiae . FEBS Lett 349:275–280 [CrossRef]
     [Google Scholar]
  30. Tsukada M., Ohsumi Y. 1993; Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae . FEBS Lett 333:169–174 [CrossRef]
     [Google Scholar]
  31. Veses V., Casanova M., Murgui A., Dominguez A., Gow N. A., Martinez J. P. 2005; ABG1, a novel and essential Candida albicans gene encoding a vacuolar protein involved in cytokinesis and hyphal branching. Eukaryot Cell 4:1088–1101 [CrossRef]
     [Google Scholar]
  32. Vida T. A., Emr S. D. 1995; A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast. J Cell Biol 128:779–792 [CrossRef]
     [Google Scholar]
  33. Wang C. W., Klionsky D. J. 2003; The molecular mechanism of autophagy. Mol Med 9:65–76
     [Google Scholar]
  34. Wilson R. B., Davis D., Mitchell A. P. 1999; Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol 181:1868–1874
     [Google Scholar]
  35. Yorimitsu T., Klionsky D. J. 2005; Autophagy: molecular machinery for self-eating. Cell Death Differ 12 :Suppl. 21542–1552 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2006/001610-0
Loading
Autophagy in the pathogen Candida albicans
Microbiology 153, 51 (2007); https://doi.org/10.1099/mic.0.2006/001610-0
/content/journal/micro/10.1099/mic.0.2006/001610-0
/content/journal/micro/10.1099/mic.0.2006/001610-0
Loading

Data & Media loading...

Most cited 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