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 Ghannoum, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ghannoum, M. A.

 Previous Article  |  Next Article 

Clinical Microbiology Reviews, January 2000, p. 122-143, Vol. 13, No. 1
0893-8512/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Potential Role of Phospholipases in Virulence and Fungal Pathogenesis

Mahmoud A. Ghannoum*

Center for Medical Mycology, Mycology Reference Laboratory, University Hospitals of Cleveland, and Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106-5028

Microbial pathogens use a number of genetic strategies to invade the host and cause infection. These common themes are found throughout microbial systems. Secretion of enzymes, such as phospholipase, has been proposed as one of these themes that are used by bacteria, parasites, and pathogenic fungi. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus, has gained credence recently. In this review, data implicating phospholipase as a virulence factor in C. albicans, Candida glabrata, C. neoformans, and A. fumigatus are presented. A detailed description of the molecular and biochemical approaches used to more definitively delineate the role of phospholipase in the virulence of C. albicans is also covered. These approaches resulted in cloning of three genes encoding candidal phospholipases (caPLP1, caPLB2, and PLD). By using targeted gene disruption, C. albicans null mutants that failed to secrete phospholipase B, encoded by caPLB1, were constructed. When these isogenic strain pairs were tested in two clinically relevant murine models of candidiasis, deletion of caPLB1 was shown to lead to attenuation of candidal virulence. Importantly, immunogold electron microscopy studies showed that C. albicans secretes this enzyme during the infectious process. These data indicate that phospholipase B is essential for candidal virulence. Although the mechanism(s) through which phospholipase modulates fungal virulence is still under investigations, early data suggest that direct host cell damage and lysis are the main mechanisms contributing to fungal virulence. Since the importance of phospholipases in fungal virulence is already known, the next challenge will be to utilize these lytic enzymes as therapeutic and diagnostic targets.

* Mailing address: Center for Medical Mycology, Mycology Reference Laboratory, University Hospitals of Cleveland and Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106-5028. Phone: (216) 844 8580. Fax: (216) 844 1076. E-mail: mag3{at}po.cwru.edu.

Clinical Microbiology Reviews, January 2000, p. 122-143, Vol. 13, No. 1
0893-8512/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Sharpton, T. J., Stajich, J. E., Rounsley, S. D., Gardner, M. J., Wortman, J. R., Jordar, V. S., Maiti, R., Kodira, C. D., Neafsey, D. E., Zeng, Q., Hung, C.-Y., McMahan, C., Muszewska, A., Grynberg, M., Mandel, M. A., Kellner, E. M., Barker, B. M., Galgiani, J. N., Orbach, M. J., Kirkland, T. N., Cole, G. T., Henn, M. R., Birren, B. W., Taylor, J. W. (2009). Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives. Genome Res 19: 1722-1731 [Abstract] [Full Text]  
  • Polakova, S., Blume, C., Zarate, J. A., Mentel, M., Jorck-Ramberg, D., Stenderup, J., Piskur, J. (2009). Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata. Proc. Natl. Acad. Sci. USA 106: 2688-2693 [Abstract] [Full Text]  
  • Mao, Y., Zhang, Z., Gast, C., Wong, B. (2008). C-Terminal Signals Regulate Targeting of Glycosylphosphatidylinositol-Anchored Proteins to the Cell Wall or Plasma Membrane in Candida albicans. Eukaryot Cell 7: 1906-1915 [Abstract] [Full Text]  
  • Trofa, D., Gacser, A., Nosanchuk, J. D. (2008). Candida parapsilosis, an Emerging Fungal Pathogen. Clin. Microbiol. Rev. 21: 606-625 [Abstract] [Full Text]  
  • Chaffin, W. L. (2008). Candida albicans Cell Wall Proteins. Microbiol. Mol. Biol. Rev. 72: 495-544 [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]  
  • Li, L., Redding, S., Dongari-Bagtzoglou, A. (2007). Candida glabrata, an Emerging Oral Opportunistic Pathogen. JDR 86: 204-215 [Abstract] [Full Text]  
  • Rydkina, E., Sahni, A., Baggs, R. B., Silverman, D. J., Sahni, S. K. (2006). Infection of Human Endothelial Cells with Spotted Fever Group Rickettsiae Stimulates Cyclooxygenase 2 Expression and Release of Vasoactive Prostaglandins. Infect. Immun. 74: 5067-5074 [Abstract] [Full Text]  
  • Istivan, T. S., Coloe, P. J. (2006). Phospholipase A in Gram-negative bacteria and its role in pathogenesis.. Microbiology 152: 1263-1274 [Abstract] [Full Text]  
  • da Silva, E. G., Baroni, F. d. A., Viani, F. C., Ruiz, L. d. S., Gandra, R. F., Auler, M. E., Dias, A. L. T., Gambale, W., Paula, C. R. (2006). Virulence profile of strains of Cryptococcus neoformans var. grubii evaluated by experimental infection in BALB/c mice and correlation with exoenzyme activity. J Med Microbiol 55: 139-142 [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]  
  • Kunze, D., Melzer, I., Bennett, D., Sanglard, D., MacCallum, D., Norskau, J., Coleman, D. C., Odds, F. C., Schafer, W., Hube, B. (2005). Functional analysis of the phospholipase C gene CaPLC1 and two unusual phospholipase C genes, CaPLC2 and CaPLC3, of Candida albicans. Microbiology 151: 3381-3394 [Abstract] [Full Text]  
  • Villar, C. C., Kashleva, H., Mitchell, A. P., Dongari-Bagtzoglou, A. (2005). Invasive Phenotype of Candida albicans Affects the Host Proinflammatory Response to Infection. Infect. Immun. 73: 4588-4595 [Abstract] [Full Text]  
  • Yordanov, M, Dimitrova, P, Patkar, S, Falcocchio, S, Xoxi, E, Saso, L, Ivanovska, N (2005). Ibogaine reduces organ colonization in murine systemic and gastrointestinal Candida albicans infections. J Med Microbiol 54: 647-653 [Abstract] [Full Text]  
  • Samaranayake, Y H, Dassanayake, R S, Jayatilake, J A., Cheung, B P., Yau, J Y., Yeung, K W., Samaranayake, L P (2005). Phospholipase B enzyme expression is not associated with other virulence attributes in Candida albicans isolates from patients with human immunodeficiency virus infection. J Med Microbiol 54: 583-593 [Abstract] [Full Text]  
  • Taylor, B. N., Staib, P., Binder, A., Biesemeier, A., Sehnal, M., Rollinghoff, M., Morschhauser, J., Schroppel, K. (2005). Profile of Candida albicans-Secreted Aspartic Proteinase Elicited during Vaginal Infection. Infect. Immun. 73: 1828-1835 [Abstract] [Full Text]  
  • de Repentigny, L., Lewandowski, D., Jolicoeur, P. (2004). Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection. Clin. Microbiol. Rev. 17: 729-759 [Abstract] [Full Text]  
  • Tang, N., Liu, L., Kang, K., Mukherjee, P. K., Takahara, M., Chen, G., McCormick, T. S., Cooper, K. D., Ghannoum, M. (2004). Inhibition of Monocytic Interleukin-12 Production by Candida albicans via Selective Activation of ERK Mitogen-Activated Protein Kinase. Infect. Immun. 72: 2513-2520 [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]  
  • 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]  
  • Timpe, J. M., Holm, M. M., Vanlerberg, S. L., Basrur, V., Lafontaine, E. R. (2003). Identification of a Moraxella catarrhalis Outer Membrane Protein Exhibiting Both Adhesin and Lipolytic Activities. Infect. Immun. 71: 4341-4350 [Abstract] [Full Text]  
  • Noverr, M. C., Erb-Downward, J. R., Huffnagle, G. B. (2003). Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes. Clin. Microbiol. Rev. 16: 517-533 [Abstract] [Full Text]  
  • Sitheeque, M.A.M., Samaranayake, L.P. (2003). CHRONIC HYPERPLASTIC CANDIDOSIS/CANDIDIASIS (CANDIDAL LEUKOPLAKIA). CROBM 14: 253-267 [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]  
  • Noverr, M. C., Cox, G. M., Perfect, J. R., Huffnagle, G. B. (2003). Role of PLB1 in Pulmonary Inflammation and Cryptococcal Eicosanoid Production. Infect. Immun. 71: 1538-1547 [Abstract] [Full Text]  
  • Mukherjee, P. K., Chandra, J., Kuhn, D. M., Ghannoum, M. A. (2003). Differential expression of Candida albicans phospholipase B (PLB1) under various environmental and physiological conditions. Microbiology 149: 261-267 [Abstract] [Full Text]  
  • Inglis, D. O., Johnson, A. D. (2002). Ash1 Protein, an Asymmetrically Localized Transcriptional Regulator, Controls Filamentous Growth and Virulence of Candida albicans. Mol. Cell. Biol. 22: 8669-8680 [Abstract] [Full Text]  
  • Nauze, M., Gonin, L., Chaminade, B., Peres, C., Hullin-Matsuda, F., Perret, B., Chap, H., Gassama-Diagne, A. (2002). Guinea Pig Phospholipase B, Identification of the Catalytic Serine and the Proregion Involved in Its Processing and Enzymatic Activity. J. Biol. Chem. 277: 44093-44099 [Abstract] [Full Text]  
  • Ripeau, J.-S., Aumont, F., Belhumeur, P., Ostrosky-Zeichner, L., Rex, J. H., de Repentigny, L. (2002). Effect of the Echinocandin Caspofungin on Expression of Candida albicans Secretory Aspartyl Proteinases and Phospholipase In Vitro. Antimicrob. Agents Chemother. 46: 3096-3100 [Abstract] [Full Text]  
  • Noverr, M. C., Toews, G. B., Huffnagle, G. B. (2002). Production of Prostaglandins and Leukotrienes by Pathogenic Fungi. Infect. Immun. 70: 400-402 [Abstract] [Full Text]  
  • Barchiesi, F., Schimizzi, A. M., Caselli, F., Giannini, D., Camiletti, V., Fileni, B., Giacometti, A., Di Francesco, L. F., Scalise, G. (2001). Activity of the new antifungal triazole, posaconazole, against Cryptococcus neoformans. J Antimicrob Chemother 48: 769-773 [Abstract] [Full Text]  
  • Gottfredsson, M., Jessup, C. J., Cox, G. M., Perfect, J. R., Ghannoum, M. A. (2001). Fungal Phospholipase Activity and Susceptibility to Lipid Preparations of Amphotericin B. Antimicrob. Agents Chemother. 45: 3231-3233 [Abstract] [Full Text]  
  • Mukherjee, P. K., Seshan, K. R., Leidich, S. D., Chandra, J., Cole, G. T., Ghannoum, M. A. (2001). Reintroduction of the PLB1 gene into Candida albicans restores virulence in vivo. Microbiology 147: 2585-2597 [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]  
  • Chang, Y. C., Penoyer, L. A., Kwon-Chung, K. J. (2001). The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. Proc. Natl. Acad. Sci. USA 10.1073/pnas.061031998v1 [Abstract] [Full Text]  
  • Slifkin, M. (2000). Tween 80 Opacity Test Responses of Various Candida Species. J. Clin. Microbiol. 38: 4626-4628 [Abstract] [Full Text]  
  • Davis, D., Edwards, J. E. Jr., Mitchell, A. P., Ibrahim, A. S. (2000). Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions. Infect. Immun. 68: 5953-5959 [Abstract] [Full Text]  
  • Chang, Y. C., Penoyer, L. A., Kwon-Chung, K. J. (2001). The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. Proc. Natl. Acad. Sci. USA 98: 3258-3263 [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»