This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanglard, D. Articles by Gow, N. A. Search for Related Content PubMed PubMed Citation Articles by Sanglard, D. Articles by Gow, N. A.

 Previous Article  |  Next Article 

Infect. Immun., Sep 1997, 3539-3546, Vol 65, No. 9
Copyright © 1997, American Society for Microbiology

A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans causes attenuated virulence

D Sanglard, B Hube, M Monod, FC Odds and NA Gow
Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. dsanglar@eliot.unil.ch

Secreted aspartyl proteinases (Saps) from Candida albicans are encoded by a multigene family with at least nine members (SAP1 to SAP9) and are considered putative virulence factors important for the pathogenicity of this human pathogen. The role of Sap isoenzymes in the virulence of C. albicans has not yet been clearly established, and therefore, using recent progress in the genetics of this yeast, we have constructed a panel of isogenic yeasts, each with a disruption of one or several SAP genes. We focused on the construction of a C. albicans strain in which three related SAP genes (SAP4, SAP5, and SAP6) were disrupted. Growth of the delta sap4,5,6 triple homozygous null mutant DSY459 in complex medium was not affected, whereas, interestingly, growth in a medium containing protein as the sole nitrogen source was severely impaired compared to the growth of the wild-type parent strain SC5314. Since the presence of Sap2 is required for optimal growth on such medium, this suggests that Sap4, Sap5, or Sap6 plays an important role for the process of induction of SAP2. When guinea pigs and mice were injected intravenously with DSY459, their survival time was significantly longer than that of control animals infected with the wild-type SC5314. Attenuated virulence of DSY459 was followed by a significant reduction of yeast cells in infected organs. These data suggest that the group of Sap4, Sap5, and Sap6 isoenzymes is important for the normal progression of systemic infection by C. albicans in animals.

This article has been cited by other articles:

• Naglik, J. R., Moyes, D., Makwana, J., Kanzaria, P., Tsichlaki, E., Weindl, G., Tappuni, A. R., Rodgers, C. A., Woodman, A. J., Challacombe, S. J., Schaller, M., Hube, B. (2008). Quantitative expression of the Candida albicans secreted aspartyl proteinase gene family in human oral and vaginal candidiasis. Microbiology 154: 3266-3280 [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]  
• Chaffin, W. L. (2008). Candida albicans Cell Wall Proteins. Microbiol. Mol. Biol. Rev. 72: 495-544 [Abstract] [Full Text]  
• Banerjee, M., Thompson, D. S., Lazzell, A., Carlisle, P. L., Pierce, C., Monteagudo, C., Lopez-Ribot, J. L., Kadosh, D. (2008). UME6, a Novel Filament-specific Regulator of Candida albicans Hyphal Extension and Virulence. Mol. Biol. Cell 19: 1354-1365 [Abstract] [Full Text]  
• Fu, Y., Luo, G., Spellberg, B. J., Edwards, J. E. Jr., Ibrahim, A. S. (2008). Gene Overexpression/Suppression Analysis of Candidate Virulence Factors of Candida albicans. Eukaryot Cell 7: 483-492 [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]  
• Schaefer, D., Cote, P., Whiteway, M., Bennett, R. J. (2007). Barrier Activity in Candida albicans Mediates Pheromone Degradation and Promotes Mating. Eukaryot Cell 6: 907-918 [Abstract] [Full Text]  
• Villar, C. C., Kashleva, H., Nobile, C. J., Mitchell, A. P., Dongari-Bagtzoglou, A. (2007). Mucosal Tissue Invasion by Candida albicans Is Associated with E-Cadherin Degradation, Mediated by Transcription Factor Rim101p and Protease Sap5p. Infect. Immun. 75: 2126-2135 [Abstract] [Full Text]  
• Kunze, D., MacCallum, D., Odds, F. C., Hube, B. (2007). Multiple functions of DOA1 in Candida albicans. Microbiology 153: 1026-1041 [Abstract] [Full Text]  
• Martinez, P., Ljungdahl, P. O. (2005). Divergence of Stp1 and Stp2 Transcription Factors in Candida albicans Places Virulence Factors Required for Proper Nutrient Acquisition under Amino Acid Control. Mol. Cell. Biol. 25: 9435-9446 [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]  
• Kadosh, D., Johnson, A. D. (2005). Induction of the Candida albicans Filamentous Growth Program by Relief of Transcriptional Repression: A Genome-wide Analysis. Mol. Biol. Cell 16: 2903-2912 [Abstract] [Full Text]  
• Schaller, M., Korting, H. C., Borelli, C., Hamm, G., Hube, B. (2005). Candida albicans-Secreted Aspartic Proteinases Modify the Epithelial Cytokine Response in an In Vitro Model of Vaginal Candidiasis. Infect. Immun. 73: 2758-2765 [Abstract] [Full Text]  
• Copping, V. M. S., Barelle, C. J., Hube, B., Gow, N. A. R., Brown, A. J. P., Odds, F. C. (2005). Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes. J Antimicrob Chemother 55: 645-654 [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]  
• Rowbottom, L., Munro, C. A., Gow, N. A. R. (2004). Candida albicans mutants in the BNI4 gene have reduced cell-wall chitin and alterations in morphogenesis. Microbiology 150: 3243-3252 [Abstract] [Full Text]  
• Moran, G., Stokes, C., Thewes, S., Hube, B., Coleman, D. C., Sullivan, D. (2004). Comparative genomics using Candida albicans DNA microarrays reveals absence and divergence of virulence-associated genes in Candida dubliniensis. Microbiology 150: 3363-3382 [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]  
• Martin, S. W., Konopka, J. B. (2004). Lipid Raft Polarization Contributes to Hyphal Growth in Candida albicans. Eukaryot Cell 3: 675-684 [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]  
• 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]  
• Sanchez, A. A., Johnston, D. A., Myers, C., Edwards, J. E. Jr., Mitchell, A. P., Filler, S. G. (2004). Relationship between Candida albicans Virulence during Experimental Hematogenously Disseminated Infection and Endothelial Cell Damage In Vitro. Infect. Immun. 72: 598-601 [Abstract] [Full Text]  
• Borst, A., Fluit, A. C. (2003). High levels of hydrolytic enzymes secreted by Candida albicans isolates involved in respiratory infections. J Med Microbiol 52: 971-974 [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]  
• Jong, A. Y., Chen, S. H. M., Stins, M. F., Kim, K. S., Tuan, T.-L., Huang, S.-H. (2003). Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells. J Med Microbiol 52: 615-622 [Abstract] [Full Text]  
• Schaller, M., Bein, M., Korting, H. C., Baur, S., Hamm, G., Monod, M., Beinhauer, S., Hube, B. (2003). The Secreted Aspartyl Proteinases Sap1 and Sap2 Cause Tissue Damage in an In Vitro Model of Vaginal Candidiasis Based on Reconstituted Human Vaginal Epithelium. Infect. Immun. 71: 3227-3234 [Abstract] [Full Text]  
• Blankenship, J. R., Wormley, F. L., Boyce, M. K., Schell, W. A., Filler, S. G., Perfect, J. R., Heitman, J. (2003). Calcineurin Is Essential for Candida albicans Survival in Serum and Virulence. Eukaryot Cell 2: 422-430 [Abstract] [Full Text]  
• Newport, G., Kuo, A., Flattery, A., Gill, C., Blake, J. J., Kurtz, M. B., Abruzzo, G. K., Agabian, N. (2003). Inactivation of Kex2p Diminishes the Virulence of Candida albicans. J. Biol. Chem. 278: 1713-1720 [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]  
• Heymann, P., Gerads, M., Schaller, M., Dromer, F., Winkelmann, G., Ernst, J. F. (2002). The Siderophore Iron Transporter of Candida albicans (Sit1p/Arn1p) Mediates Uptake of Ferrichrome-Type Siderophores and Is Required for Epithelial Invasion. Infect. Immun. 70: 5246-5255 [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]  
• Van Dijck, P., De Rop, L., Szlufcik, K., Van Ael, E., Thevelein, J. M. (2002). Disruption of the Candida albicans TPS2 Gene Encoding Trehalose-6-Phosphate Phosphatase Decreases Infectivity without Affecting Hypha Formation. Infect. Immun. 70: 1772-1782 [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]  
• Jong, A. Y., Stins, M. F., Huang, S.-H., Chen, S. H. M., Kim, K. S. (2001). Traversal of Candida albicans across Human Blood-Brain Barrier In Vitro. Infect. Immun. 69: 4536-4544 [Abstract] [Full Text]  
• Lee, S. A., Mao, Y., Zhang, Z., Wong, B. (2001). Overexpression of a dominant-negative allele of YPT1 inhibits growth and aspartyl protease secretion in Candida albicans. Microbiology 147: 1961-1970 [Abstract] [Full Text]  
• Hoyer, L. L., Fundyga, R., Hecht, J. E., Kapteyn, J. C., Klis, F. M., Arnold, J. (2001). Characterization of Agglutinin-like Sequence Genes From Non-albicans Candida and Phylogenetic Analysis of the ALS Family. Genetics 157: 1555-1567 [Abstract] [Full Text]  
• Schroppel, K., Spro{beta}er, K., Whiteway, M., Thomas, D. Y., Rollinghoff, M., Csank, C. (2000). Repression of Hyphal Proteinase Expression by the Mitogen-Activated Protein (MAP) Kinase Phosphatase Cpp1p of Candida albicans Is Independent of the MAP Kinase Cek1p. Infect. Immun. 68: 7159-7161 [Abstract] [Full Text]  
• Odds, F. C., Van Nuffel, L., Gow, N. A. R. (2000). Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host. Microbiology 146: 1881-1889 [Abstract] [Full Text]  
• RUMA-HAYNES, P., BROWNLEE, A. G., SORRELL, T. C. (2000). A rapid method for detecting extracellular proteinase activity in Cryptococcus neoformans and a survey of 63 isolates. J Med Microbiol 49: 733-737 [Abstract] [Full Text]  
• Ramanan, N., Wang, Y. (2000). A High-Affinity Iron Permease Essential for Candida albicans Virulence. Science 288: 1062-1064 [Abstract] [Full Text]  
• Wu, T., Wright, K., Hurst, S. F., Morrison, C. J. (2000). Enhanced Extracellular Production of Aspartyl Proteinase, a Virulence Factor, by Candida albicans Isolates following Growth in Subinhibitory Concentrations of Fluconazole. Antimicrob. Agents Chemother. 44: 1200-1208 [Abstract] [Full Text]  
• O’Day, D. M., Head, W. S., Csank, C., Shetlar, D. J., Robinson, R. D., McCollum, G. W., Yang, R., Zhu, T. L., Wang, M. X. (2000). Differences in Virulence between Two Candida albicans Strains in Experimental Keratitis. IOVS 41: 1116-1121 [Abstract] [Full Text]  
• Ghannoum, M. A. (2000). Potential Role of Phospholipases in Virulence and Fungal Pathogenesis. Clin. Microbiol. Rev. 13: 122-143 [Abstract] [Full Text]  
• Kretschmar, M., Hube, B., Bertsch, T., Sanglard, D., Merker, R., Schroder, M., Hof, H., Nichterlein, T. (1999). Germ Tubes and Proteinase Activity Contribute to Virulence of Candida albicans in Murine Peritonitis. Infect. Immun. 67: 6637-6642 [Abstract] [Full Text]  
• Mao, Y., Kalb, V. F., Wong, B. (1999). Overexpression of a Dominant-Negative Allele of SEC4 Inhibits Growth and Protein Secretion in Candida albicans. J. Bacteriol. 181: 7235-7242 [Abstract] [Full Text]  
• Korting, H. C., Schaller, M., Eder, G., Hamm, G., Böhmer, U., Hube, B. (1999). Effects of the Human Immunodeficiency Virus (HIV) Proteinase Inhibitors Saquinavir and Indinavir on In Vitro Activities of Secreted Aspartyl Proteinases of Candida albicans Isolates from HIV-Infected Patients. Antimicrob. Agents Chemother. 43: 2038-2042 [Abstract] [Full Text]  
• Rieg, G., Fu, Y., Ibrahim, A. S., Zhou, X., Filler, S. G., Edwards, J. E. Jr. (1999). Unanticipated Heterogeneity in Growth Rate and Virulence among Candida albicans AAF1 Null Mutants. Infect. Immun. 67: 3193-3198 [Abstract] [Full Text]  
• Naglik, J. R., Newport, G., White, T. C., Fernandes-Naglik, L. L., Greenspan, J. S., Greenspan, D., Sweet, S. P., Challacombe, S. J., Agabian, N. (1999). In Vivo Analysis of Secreted Aspartyl Proteinase Expression in Human Oral Candidiasis. Infect. Immun. 67: 2482-2490 [Abstract] [Full Text]  
• Leidich, S. D., Ibrahim, A. S., Fu, Y., Koul, A., Jessup, C., Vitullo, J., Fonzi, W., Mirbod, F., Nakashima, S., Nozawa, Y., Ghannoum, M. A. (1998). Cloning and Disruption of caPLB1, a Phospholipase B Gene Involved in the Pathogenicity of Candida albicans. J. Biol. Chem. 273: 26078-26086 [Abstract] [Full Text]  
• Buurman, E. T., Westwater, C., Hube, B., Brown, A. J. P., Odds, F. C., Gow, N. A. R. (1998). Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans. Proc. Natl. Acad. Sci. USA 95: 7670-7675 [Abstract] [Full Text]  
• Csank, C., Schroppel, K., Leberer, E., Harcus, D., Mohamed, O., Meloche, S., Thomas, D. Y., Whiteway, M. (1998). Roles of the Candida albicans Mitogen-Activated Protein Kinase Homolog, Cek1p, in Hyphal Development and Systemic Candidiasis. Infect. Immun. 66: 2713-2721 [Abstract] [Full Text]  
• Ibrahim, A. S., Filler, S. G., Sanglard, D., Edwards, J. E. Jr., Hube, B. (1998). Secreted Aspartyl Proteinases and Interactions of Candida albicans with Human Endothelial Cells. Infect. Immun. 66: 3003-3005 [Abstract] [Full Text]  
• Chaffin, W. L., Lopez-Ribot, J. L., Casanova, M., Gozalbo, D., Martinez, J. P. (1998). Cell Wall and Secreted Proteins of Candida albicans: Identification, Function, and Expression. Microbiol. Mol. Biol. Rev. 62: 130-180 [Abstract] [Full Text]