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. 1995 May;63(5):1993–1998. doi: 10.1128/iai.63.5.1993-1998.1995

Evidence implicating phospholipase as a virulence factor of Candida albicans.

A S Ibrahim 1, F Mirbod 1, S G Filler 1, Y Banno 1, G T Cole 1, Y Kitajima 1, J E Edwards Jr 1, Y Nozawa 1, M A Ghannoum 1
PMCID: PMC173255  PMID: 7729913

Abstract

Three different approaches were used to investigate the role of extracellular phospholipases in the pathogenicity of Candida albicans. First, we compared 11 blood isolates of this yeast with an equal number of commensal strains isolated from the oral cavities of healthy volunteers. Blood isolates produced significantly more extracellular phospholipase activity than the commensal strains did. Second, two clinical isolates of C. albicans that differed in their levels of virulence in a newborn mouse model were compared for their ability to secrete phospholipases. The invasive strain produced significantly more extracellular phospholipase activity than the noninvasive strain did. Third, nine blood isolates were characterized for their phospholipase and proteinase production, germ tube formation, growth, and adherence to and damage of endothelial cells in vitro. These factors were analyzed subsequently to determine whether they predicted mortality in a mouse model of hematogenously disseminated candidiasis. By proportional hazard analysis, the relative risk of death was 5.6-fold higher (95% confidence interval, 1.672 to 18.84 [P < 0.005]) in the mice infected with the higher-phospholipase-secreting strains than in the low-phospholipase secretors. None of the other putative virulence factors predicted mortality. Characterization of phospholipases secreted by three of the blood isolates showed that these strains secreted both phospholipase B and lysophospholipase-transacylase activities. These results implicate extracellular phospholipase as a virulence factor in the pathogenesis of hematogenous infections caused by C. albicans.

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Selected References

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  1. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  2. Banno Y., Yamada T., Nozawa Y. Secreted phospholipases of the dimorphic fungus, Candida albicans; separation of three enzymes and some biological properties. Sabouraudia. 1985 Feb;23(1):47–54. doi: 10.1080/00362178585380081. [DOI] [PubMed] [Google Scholar]
  3. Barrett-Bee K., Hayes Y., Wilson R. G., Ryley J. F. A comparison of phospholipase activity, cellular adherence and pathogenicity of yeasts. J Gen Microbiol. 1985 May;131(5):1217–1221. doi: 10.1099/00221287-131-5-1217. [DOI] [PubMed] [Google Scholar]
  4. Cole G. T., Lynn K. T., Seshan K. R. An animal model for oropharyngeal, esophageal and gastric candidosis. Mycoses. 1990 Jan;33(1):7–19. doi: 10.1111/myc.1990.33.1.7. [DOI] [PubMed] [Google Scholar]
  5. Cutler J. E. Putative virulence factors of Candida albicans. Annu Rev Microbiol. 1991;45:187–218. doi: 10.1146/annurev.mi.45.100191.001155. [DOI] [PubMed] [Google Scholar]
  6. Falo L. D., Jr, Benacerraf B., Rock K. L. Phospholipase treatment of accessory cells that have been exposed to antigen selectively inhibits antigen-specific Ia-restricted, but not allospecific, stimulation of T lymphocytes. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6994–6997. doi: 10.1073/pnas.83.18.6994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Falo L. D., Jr, Haber S. I., Herrmann S., Benacerraf B., Rock K. L. Characterization of antigen association with accessory cells: specific removal of processed antigens from the cell surface by phospholipases. Proc Natl Acad Sci U S A. 1987 Jan;84(2):522–526. doi: 10.1073/pnas.84.2.522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Filler S. G., Ibe B. O., Ibrahim A. S., Ghannoum M. A., Raj J. U., Edwards J. E., Jr Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis. Infect Immun. 1994 Mar;62(3):1064–1069. doi: 10.1128/iai.62.3.1064-1069.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Geoffroy C., Raveneau J., Beretti J. L., Lecroisey A., Vazquez-Boland J. A., Alouf J. E., Berche P. Purification and characterization of an extracellular 29-kilodalton phospholipase C from Listeria monocytogenes. Infect Immun. 1991 Jul;59(7):2382–2388. doi: 10.1128/iai.59.7.2382-2388.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ghannoum M. A., Filler S. G., Ibrahim A. S., Fu Y., Edwards J. E., Jr Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B. Antimicrob Agents Chemother. 1992 Oct;36(10):2239–2244. doi: 10.1128/aac.36.10.2239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ibrahim A. S., Filler S. G., Ghannoum M. A., Edwards J. E., Jr Interferon-gamma protects endothelial cells from damage by Candida albicans. J Infect Dis. 1993 Jun;167(6):1467–1470. doi: 10.1093/infdis/167.6.1467. [DOI] [PubMed] [Google Scholar]
  12. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Janda J. M., Bottone E. J. Pseudomonas aeruginosa enzyme profiling: predictor of potential invasiveness and use as an epidemiological tool. J Clin Microbiol. 1981 Jul;14(1):55–60. doi: 10.1128/jcm.14.1.55-60.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee K. S., Patton J. L., Fido M., Hines L. K., Kohlwein S. D., Paltauf F., Henry S. A., Levin D. E. The Saccharomyces cerevisiae PLB1 gene encodes a protein required for lysophospholipase and phospholipase B activity. J Biol Chem. 1994 Aug 5;269(31):19725–19730. [PubMed] [Google Scholar]
  15. Macdonald F., Odds F. C. Inducible proteinase of Candida albicans in diagnostic serology and in the pathogenesis of systemic candidosis. J Med Microbiol. 1980 Aug;13(3):423–435. doi: 10.1099/00222615-13-3-423. [DOI] [PubMed] [Google Scholar]
  16. Marques M. B., Weller P. F., Parsonnet J., Ransil B. J., Nicholson-Weller A. Phosphatidylinositol-specific phospholipase C, a possible virulence factor of Staphylococcus aureus. J Clin Microbiol. 1989 Nov;27(11):2451–2454. doi: 10.1128/jcm.27.11.2451-2454.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Marrie T. J., Costerton J. W. The ultrastructure of Candida albicans infections. Can J Microbiol. 1981 Nov;27(11):1156–1164. doi: 10.1139/m81-181. [DOI] [PubMed] [Google Scholar]
  18. Pugh D., Cawson R. A. The cytochemical localization of phospholipase in Candida albicans infecting the chick chorio-allantoic membrane. Sabouraudia. 1977 Mar;15(1):29–35. [PubMed] [Google Scholar]
  19. Ravdin J. I., Murphy C. F., Guerrant R. L., Long-Krug S. A. Effect of antagonists of calcium and phospholipase A on the cytopathogenicity of Entamoeba histolytica. J Infect Dis. 1985 Sep;152(3):542–549. doi: 10.1093/infdis/152.3.542. [DOI] [PubMed] [Google Scholar]
  20. Saffer L. D., Long Krug S. A., Schwartzman J. D. The role of phospholipase in host cell penetration by Toxoplasma gondii. Am J Trop Med Hyg. 1989 Feb;40(2):145–149. doi: 10.4269/ajtmh.1989.40.145. [DOI] [PubMed] [Google Scholar]
  21. Samaranayake L. P., Raeside J. M., MacFarlane T. W. Factors affecting the phospholipase activity of Candida species in vitro. Sabouraudia. 1984;22(3):201–207. [PubMed] [Google Scholar]
  22. Silverman D. J., Santucci L. A., Meyers N., Sekeyova Z. Penetration of host cells by Rickettsia rickettsii appears to be mediated by a phospholipase of rickettsial origin. Infect Immun. 1992 Jul;60(7):2733–2740. doi: 10.1128/iai.60.7.2733-2740.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takahashi M., Banno Y., Nozawa Y. Secreted Candida albicans phospholipases: purification and characterization of two forms of lysophospholipase-transacylase. J Med Vet Mycol. 1991;29(3):193–204. [PubMed] [Google Scholar]
  24. Titball R. W., Hunter S. E., Martin K. L., Morris B. C., Shuttleworth A. D., Rubidge T., Anderson D. W., Kelly D. C. Molecular cloning and nucleotide sequence of the alpha-toxin (phospholipase C) of Clostridium perfringens. Infect Immun. 1989 Feb;57(2):367–376. doi: 10.1128/iai.57.2.367-376.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Walker D. H., Firth W. T., Ballard J. G., Hegarty B. C. Role of phospholipase-associated penetration mechanism in cell injury by Rickettsia rickettsii. Infect Immun. 1983 May;40(2):840–842. doi: 10.1128/iai.40.2.840-842.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Werner H. Untersuchungen über die Lipase-Aktivität bei Hefen und hefeähnlichen Pilzen. Zentralbl Bakteriol Orig. 1966 May;200(1):113–124. [PubMed] [Google Scholar]
  27. Winkler H. H., Miller E. T. Phospholipase A activity in the hemolysis of sheep and human erythrocytes by Rickettsia prowazeki. Infect Immun. 1980 Aug;29(2):316–321. doi: 10.1128/iai.29.2.316-321.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wright G. C., Weiss J., Kim K. S., Verheij H., Elsbach P. Bacterial phospholipid hydrolysis enhances the destruction of Escherichia coli ingested by rabbit neutrophils. Role of cellular and extracellular phospholipases. J Clin Invest. 1990 Jun;85(6):1925–1935. doi: 10.1172/JCI114655. [DOI] [PMC free article] [PubMed] [Google Scholar]

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