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 Kretschmar, M.
Right arrow Articles by Nichterlein, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kretschmar, M.
Right arrow Articles by Nichterlein, T.

 Previous Article  |  Next Article 

Infection and Immunity, December 1999, p. 6637-6642, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Germ Tubes and Proteinase Activity Contribute to Virulence of Candida albicans in Murine Peritonitis

Marianne Kretschmar,1 Bernhard Hube,2 Thomas Bertsch,3 Dominique Sanglard,4 Renate Merker,5 Meike Schröder,1 Herbert Hof,1 and Thomas Nichterlein1,*

Institute of Medical Microbiology and Hygiene1 and Institute of Clinical Chemistry,3 Faculty of Clinical Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Institute for General Botany, Applied Molecular Biology III, University of Hamburg, 22609 Hamburg,2 and Department of Electrical Engineering IEE, University of Technology, 01062 Dresden,5 Germany, and Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland4

Received 7 June 1999/Returned for modification 6 July 1999/Accepted 27 August 1999

Peritonitis with Candida albicans is an important complication of bowel perforation and continuous ambulatory peritoneal dialysis. To define potential virulence factors, we investigated 50 strains of C. albicans in a murine peritonitis model. There was considerable variation in their virulence in this model when virulence was measured as release of organ-specific enzymes into the plasma of infected mice. Alanine aminotransferase (ALT) and alpha -amylase (AM) were used as parameters for damage of the liver and pancreas, respectively. The activities of ALT and AM in the plasma correlated with invasion into the organs measured in histologic sections and the median germ tube length induced with serum in vitro. When the activity of proteinases was inhibited in vivo with pepstatin A, there was a significant reduction of ALT and AM activities. This indicates that proteinases contributed to virulence in this model. Using strains of C. albicans with disruption of secreted aspartyl proteinase gene SAP1, SAP2, SAP3, or SAP4 through SAP6 (collectively referred to as SAP4-6), we showed that only a Delta sap4-6 triple mutant induced a significantly reduced activity of ALT in comparison to the reference strain. In contrast to the Delta sap1, Delta sap2, and Delta sap3 mutants, the ALT induced by the Delta sap4-6 mutant could not be further reduced by pepstatin A treatment, which indicates that Sap4-6 may contribute to virulence in this model.

* Corresponding author. Mailing address: Institute of Medical Microbiology and Hygiene Mannheim, Faculty of Clinical Medicine, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Phone: (49) 0621/383 2695. Fax: (49) 0621/383 3816. E-mail: thomas.nichterlein{at}imh.ma.uni-heidelberg.de.

Infection and Immunity, December 1999, p. 6637-6642, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Hornbach, A., Heyken, A., Schild, L., Hube, B., Loffler, J., Kurzai, O. (2009). The Glycosylphosphatidylinositol-Anchored Protease Sap9 Modulates the Interaction of Candida albicans with Human Neutrophils. Infect. Immun. 77: 5216-5224 [Abstract] [Full Text]  
  • Lermann, U., Morschhauser, J. (2008). Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans. Microbiology 154: 3281-3295 [Abstract] [Full Text]  
  • Staib, P., Lermann, U., Bla -Warmuth, J., Degel, B., Wurzner, R., Monod, M., Schirmeister, T., Morschhauser, J. (2008). Tetracycline-Inducible Expression of Individual Secreted Aspartic Proteases in Candida albicans Allows Isoenzyme-Specific Inhibitor Screening. Antimicrob. Agents Chemother. 52: 146-156 [Abstract] [Full Text]  
  • Jackson, B. E., Wilhelmus, K. R., Hube, B. (2007). The Role of Secreted Aspartyl Proteinases in Candida albicans Keratitis. IOVS 48: 3559-3565 [Abstract] [Full Text]  
  • Navarathna, D. H. M. L. P., Hornby, J. M., Krishnan, N., Parkhurst, A., Duhamel, G. E., Nickerson, K. W. (2007). Effect of Farnesol on a Mouse Model of Systemic Candidiasis, Determined by Use of a DPP3 Knockout Mutant of Candida albicans. Infect. Immun. 75: 1609-1618 [Abstract] [Full Text]  
  • Thewes, S., Reed, H.-K., Grosse-Siestrup, C., Groneberg, D. A., Meissler, M., Schaller, M., Hube, B. (2007). Haemoperfused liver as an ex vivo model for organ invasion of Candida albicans. J Med Microbiol 56: 266-270 [Abstract] [Full Text]  
  • Taylor, B. N., Hannemann, H., Sehnal, M., Biesemeier, A., Schweizer, A., Rollinghoff, M., Schroppel, K. (2005). Induction of SAP7 Correlates with Virulence in an Intravenous Infection Model of Candidiasis but Not in a Vaginal Infection Model in Mice. Infect. Immun. 73: 7061-7063 [Abstract] [Full Text]  
  • Tavanti, A., Pardini, G., Campa, D., Davini, P., Lupetti, A., Senesi, S. (2004). Differential Expression of Secretory Aspartyl Proteinase Genes (SAP1-10) in Oral Candida albicans Isolates with Distinct Karyotypes. J. Clin. Microbiol. 42: 4726-4734 [Abstract] [Full Text]  
  • Staib, P., Binder, A., Kretschmar, M., Nichterlein, T., Schroppel, K., Morschhauser, J. (2004). Tec1p-Independent Activation of a Hypha-Associated Candida albicans Virulence Gene during Infection. Infect. Immun. 72: 2386-2389 [Abstract] [Full Text]  
  • Morrison, C. J., Hurst, S. F., Reiss, E. (2003). Competitive Binding Inhibition Enzyme-Linked Immunosorbent Assay That Uses the Secreted Aspartyl Proteinase of Candida albicans as an Antigenic Marker for Diagnosis of Disseminated Candidiasis. CVI 10: 835-848 [Abstract] [Full Text]  
  • Naglik, J. R., Challacombe, S. J., Hube, B. (2003). Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 400-428 [Abstract] [Full Text]  
  • Chen, Y.-C., Wu, C.-C., Chung, W.-L., Lee, F.-J. S. (2002). Differential secretion of Sap4-6 proteins in Candida albicans during hyphae formation. Microbiology 148: 3743-3754 [Abstract] [Full Text]  
  • Felk, A., Kretschmar, M., Albrecht, A., Schaller, M., Beinhauer, S., Nichterlein, T., Sanglard, D., Korting, H. C., Schafer, W., Hube, B. (2002). Candida albicans Hyphal Formation and the Expression of the Efg1-Regulated Proteinases Sap4 to Sap6 Are Required for the Invasion of Parenchymal Organs. Infect. Immun. 70: 3689-3700 [Abstract] [Full Text]  
  • Staib, P., Kretschmar, M., Nichterlein, T., Hof, H., Morschhauser, J. (2002). Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the Candida albicans Virulence Gene SAP5 during Infection. Infect. Immun. 70: 921-927 [Abstract] [Full Text]  
  • Hube, B., Naglik, J. (2001). Candida albicans proteinases: resolving the mystery of a gene family. Microbiology 147: 1997-2005 [Full Text]  
  • SCHALLER, M., JANUSCHKE, E., SCHACKERT, C., WOERLE, B., KORTING, H. C. (2001). Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo. J Med Microbiol 50: 743-747 [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»