This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Van Dijck, P.
Right arrow Articles by Thevelein, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Van Dijck, P.
Right arrow Articles by Thevelein, J. M.

 Previous Article  |  Next Article 

Infection and Immunity, April 2002, p. 1772-1782, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.1772-1782.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Disruption of the Candida albicans TPS2 Gene Encoding Trehalose-6-Phosphate Phosphatase Decreases Infectivity without Affecting Hypha Formation

Patrick Van Dijck,1,2* Larissa De Rop,1 Karolina Szlufcik,1 Elke Van Ael,1 and Johan M. Thevelein1

Laboratory of Molecular Cell Biology,1 Flemish Institute for Biotechnology, Instituut voor Plantkunde en Microbiologie, Katholieke Universiteit Leuven, B-3001 Heverlee, Flanders, Belgium2

Received 6 July 2001/ Returned for modification 3 October 2001/ Accepted 20 December 2001

Deletion of trehalose-6-phosphate phosphatase, encoded by TPS2, in Saccharomyces cerevisiae results in accumulation of trehalose-6-phosphate (Tre6P) instead of trehalose under stress conditions. Since trehalose is an important stress protectant and Tre6P accumulation is toxic, we have investigated whether Tre6P phosphatase could be a useful target for antifungals in Candida albicans. We have cloned the C. albicans TPS2 (CaTPS2) gene and constructed heterozygous and homozygous deletion strains. As in S. cerevisiae, complete inactivation of Tre6P phosphatase in C. albicans results in 50-fold hyperaccumulation of Tre6P, thermosensitivity, and rapid death of the cells after a few hours at 44°C. As opposed to inactivation of Tre6P synthase by deletion of CaTPS1, deletion of CaTPS2 does not affect hypha formation on a solid glucose-containing medium. In spite of this, virulence of the homozygous deletion mutant is strongly reduced in a mouse model of systemic infection. The pathogenicity of the heterozygous deletion mutant is similar to that of the wild-type strain. CaTPS2 is a new example of a gene not required for growth under standard conditions but required for pathogenicity in a host. Our results suggest that Tre6P phosphatase may serve as a potential target for antifungal drugs. Neither Tre6P phosphatase nor its substrate is present in mammals, and assay of the enzymes is simple and easily automated for high-throughput screening.

* Corresponding author. Mailing address: Flemish Institute for Biotechnology, Katholieke Universiteit Leuven, Laboratory of Molecular Cell Biology, Kasteelpark Arenberg 31, B-3001 Heverlee, Belgium. Phone: 32-16321512. Fax: 32-16321979. E-mail: patrick.vandijck{at}bio.kuleuven.ac.be.

Editor: V. J. DiRita

Infection and Immunity, April 2002, p. 1772-1782, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.1772-1782.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ngamskulrungroj, P., Himmelreich, U., Breger, J. A., Wilson, C., Chayakulkeeree, M., Krockenberger, M. B., Malik, R., Daniel, H.-M., Toffaletti, D., Djordjevic, J. T., Mylonakis, E., Meyer, W., Perfect, J. R. (2009). The Trehalose Synthesis Pathway Is an Integral Part of the Virulence Composite for Cryptococcus gattii. Infect. Immun. 77: 4584-4596 [Abstract] [Full Text]  
  • Maidan, M. M., De Rop, L., Relloso, M., Diez-Orejas, R., Thevelein, J. M., Van Dijck, P. (2008). Combined Inactivation of the Candida albicans GPR1 and TPS2 Genes Results in Avirulence in a Mouse Model for Systemic Infection. Infect. Immun. 76: 1686-1694 [Abstract] [Full Text]  
  • Pedreno, Y., Gonzalez-Parraga, P., Martinez-Esparza, M., Sentandreu, R., Valentin, E., Arguelles, J.-C. (2007). Disruption of the Candida albicans ATC1 gene encoding a cell-linked acid trehalase decreases hypha formation and infectivity without affecting resistance to oxidative stress. Microbiology 153: 1372-1381 [Abstract] [Full Text]  
  • Enjalbert, B., MacCallum, D. M., Odds, F. C., Brown, A. J. P. (2007). Niche-Specific Activation of the Oxidative Stress Response by the Pathogenic Fungus Candida albicans. Infect. Immun. 75: 2143-2151 [Abstract] [Full Text]  
  • Petzold, E. W., Himmelreich, U., Mylonakis, E., Rude, T., Toffaletti, D., Cox, G. M., Miller, J. L., Perfect, J. R. (2006). Characterization and Regulation of the Trehalose Synthesis Pathway and Its Importance in the Pathogenicity of Cryptococcus neoformans.. Infect. Immun. 74: 5877-5887 [Abstract] [Full Text]  
  • Kingsbury, J. M., Goldstein, A. L., McCusker, J. H. (2006). Role of Nitrogen and Carbon Transport, Regulation, and Metabolism Genes for Saccharomyces cerevisiae Survival In Vivo. Eukaryot Cell 5: 816-824 [Abstract] [Full Text]  
  • Maidan, M. M., De Rop, L., Serneels, J., Exler, S., Rupp, S., Tournu, H., Thevelein, J. M., Van Dijck, P. (2005). The G Protein-coupled Receptor Gpr1 and the G{alpha} Protein Gpa2 Act through the cAMP-Protein Kinase A Pathway to Induce Morphogenesis in Candida albicans. Mol. Biol. Cell 16: 1971-1986 [Abstract] [Full Text]  
  • Pedreno, Y., Maicas, S., Arguelles, J.-C., Sentandreu, R., Valentin, E. (2004). The ATC1 Gene Encodes a Cell Wall-linked Acid Trehalase Required for Growth on Trehalose in Candida albicans. J. Biol. Chem. 279: 40852-40860 [Abstract] [Full Text]  
  • Brand, A., MacCallum, D. M., Brown, A. J. P., Gow, N. A. R., Odds, F. C. (2004). Ectopic Expression of URA3 Can Influence the Virulence Phenotypes and Proteome of Candida albicans but Can Be Overcome by Targeted Reintegration of URA3 at the RPS10 Locus. Eukaryot Cell 3: 900-909 [Abstract] [Full Text]  
  • Alarco, A.-M., Marcil, A., Chen, J., Suter, B., Thomas, D., Whiteway, M. (2004). Immune-Deficient Drosophila melanogaster: A Model for the Innate Immune Response to Human Fungal Pathogens. J. Immunol. 172: 5622-5628 [Abstract] [Full Text]  
  • Enjalbert, B., Nantel, A., Whiteway, M. (2003). Stress-induced Gene Expression in Candida albicans: Absence of a General Stress Response. Mol. Biol. Cell 14: 1460-1467 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»