1887

Abstract

Phospholipases have been proposed to contribute to the virulence of . Recently, a candidal strain deleted for , the gene encoding the predominant phospholipase B (Plb1) secreted by , was constructed and its virulence in an intravenous murine model of disseminated candidiasis was evaluated. In the present study, the gene was reintroduced back into the null mutant to generate the revertant strain, which showed similar growth and morphology to its isogenic parent strain. Virulence of the revertant strain was found to be comparable to that of the parent strain in an intravenous murine model of disseminated candidiasis. To compare the abilities of the null mutant, the revertant and the isogenic parent strains to cross the gastrointestinal (GI) tract and cause systemic infection, an oral–intragastric infant mouse model of candidiasis was used. Histological examinations and analysis of c.f.u. of the pathogen in liver homogenates revealed that the parental and revertant strains were able to invade and traverse the GI mucosa to a significantly greater extent than the null mutant. Immunofluorescence and immunoelectron microscopic studies of infected host tissue using anti-Plb1 antibody showed that Plb1 is secreted during invasion of the gastric mucosa by the parental and revertant strains. In contrast, little or no labelling was observed in the null mutant strain. The results indicate that the Plb1 secreted by enhances the ability of this organism to cross the GI tract and disseminate haematogenously. These studies provide unequivocal evidence supporting a role for Plb1 during the course of infection by .

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-147-9-2585
2001-09-01
2019-11-19
Loading full text...

Full text loading...

/deliver/fulltext/micro/147/9/1472585a.html?itemId=/content/journal/micro/10.1099/00221287-147-9-2585&mimeType=html&fmt=ahah

References

  1. Barrett-Bee, K., Hayes, Y., Wilson, R. G. & Ryley, J. F. ( 1985; ). A comparison of phospholipase activity, cellular adherence and pathogenicity of yeasts. J Gen Microbiol 131, 1217-1221.
    [Google Scholar]
  2. Boeke, J. D., LaCroute, F. & Fink, G. R. ( 1984; ). A positive selection for mutants lacking orotidine-5′-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet 197, 345-346.[CrossRef]
    [Google Scholar]
  3. Bruckmann, A., Kunkel, W., Hartl, A., Wetzker, R. & Eck, R. ( 2000; ). A phosphatidylinositol 3-kinase of Candida albicans influences adhesion, filamentous growth and virulence. Microbiology 146, 2755-2764.
    [Google Scholar]
  4. Cole, G. T., Lynn, K. T., Seshan, K. R. & Pope, L. M. ( 1989; ). Gastrointestinal and systemic candidosis in immunocompromised mice. J Med Vet Mycol 27, 363-380.[CrossRef]
    [Google Scholar]
  5. Cole, G. T., Lynn, K. T. & Seshan, K. R. ( 1990; ). An animal model for oropharyngeal, esophageal and gastric candidosis. Mycoses 33, 7-19.
    [Google Scholar]
  6. Cole, G. T., Seshan, K. R., Phaneuf, M. & Lynn, K. T. ( 1991a; ). Chlamydospore-like cells of Candida albicans in the gastrointestinal tract of infected, immunocompromised mice. Can J Microbiol 37, 637-646.[CrossRef]
    [Google Scholar]
  7. Cole, G. T., Kruse, D. & Seshan, K. R. ( 1991b; ). Antigen complex of Coccidioides immitis which elicits a precipitin antibody response in patients. Infect Immun 59, 2434-2446.
    [Google Scholar]
  8. Cole, G. T., Halawa, A. A. & Anaissie, E. J. ( 1996; ). The role of the gastrointestinal tract in hematogenous candidiasis: from the laboratory to the bedside. Clin Infect Dis 22 (suppl. 2), S73–S88.
    [Google Scholar]
  9. De Backer, M. D., de Hoogt, R. A., Froyen, G., Odds, F. C., Simons, F., Contreras, R. & Luyten, W. H. ( 2000; ). Single allele knock-out of Candida albicans CGT1 leads to unexpected resistance to hygromycin B and elevated temperature. Microbiology 146, 353-365.
    [Google Scholar]
  10. De Marie, S. ( 2000; ). New developments in the diagnosis and management of invasive fungal infections. Haematologica 85, 88-93.
    [Google Scholar]
  11. Edmond, M. B., Wallace, S. E., McClish, D. K., Pfaller, M. A., Jones, R. N. & Wenzel, R. P. ( 1999; ). Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 29, 239-244.[CrossRef]
    [Google Scholar]
  12. Falkow, S. ( 1988; ). Molecular Koch’s postulates applied to microbial pathogenicity. Rev Infect Dis 10 (suppl. 2), S274–S276.[CrossRef]
    [Google Scholar]
  13. Fonzi, W. A. & Irwin, M. Y. ( 1993; ). Isogenic strain construction and gene mapping in Candida albicans. Genetics 134, 717-728.
    [Google Scholar]
  14. Gale, C. A., Bendel, C. M., McClellan, M., Hauser, M., Becker, J. M., Berman, J. & Hostetter, M. K. ( 1998; ). Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1. Science 279, 1355-1358.[CrossRef]
    [Google Scholar]
  15. Ghannoum, M. A. ( 2000; ). Potential role of phospholipases in virulence and fungal pathogenesis. Clin Microbiol Rev 13, 122-143.[CrossRef]
    [Google Scholar]
  16. Ghannoum, M. A., Spellberg, B., Saporito-Irwin, S. M. & Fonzi, W. A. ( 1995; ). Reduced virulence of Candida albicans PHR1 mutants. Infect Immun 63, 4528-4530.
    [Google Scholar]
  17. Gillum, A. M., Tsay, E. Y. & Kirsch, D. R. ( 1984; ). Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198, 179-182.[CrossRef]
    [Google Scholar]
  18. Guentzel, M. N. & Herrera, C. ( 1982; ). Effects of compromising agents on candidosis in mice with persistent infections initiated in infancy. Infect Immun 35, 222-228.
    [Google Scholar]
  19. Howlett, J. A. & Squier, C. A. ( 1980; ). Candida albicans ultrastructure: colonization and invasion of oral epithelium. Infect Immun 29, 252-260.
    [Google Scholar]
  20. Hube, B., Ruchel, R., Monod, M., Sanglard, D. & Odds, F. C. ( 1998; ). Functional aspects of secreted Candida proteinases. Adv Exp Med Biol 436, 339-344.
    [Google Scholar]
  21. Ibrahim, A. S., Mirbod, F., Filler, S. G., Banno, Y., Cole, G. T., Kitajima, Y., Edwards, J. E.Jr, Nozawa, Y. & Ghannoum, M. A. ( 1995; ). Evidence implicating phospholipase as a virulence factor of Candida albicans. Infect Immun 63, 1993-1998.
    [Google Scholar]
  22. Jarvis, W. R. ( 1995; ). Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 20, 1526-1530.[CrossRef]
    [Google Scholar]
  23. Klepser, M. E., Lewis, R. E. & Pfaller, M. A. ( 1998; ). Therapy of Candida infections: susceptibility testing, resistance, and therapeutic options. Ann Pharmacother 32, 1353-1361.[CrossRef]
    [Google Scholar]
  24. Klotz, S. A., Drutz, D. J., Harrison, J. L. & Huppert, M. ( 1983; ). Adherence and penetration of vascular endothelium by Candida yeasts. Infect Immun 42, 374-384.
    [Google Scholar]
  25. Kruse, D. & Cole, G. T. ( 1992; ). A seroreactive 120-kilodalton β-1,3-glucanase of Coccidioides immitis which may participate in spherule morphogenesis. Infect Immun 60, 4350-4363.
    [Google Scholar]
  26. Leidich, S. D., Ibrahim, A. S., Fu, Y. & 8 other authors ( 1998; ). Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. J Biol Chem 273, 26078–26086.
    [Google Scholar]
  27. Luna, L. G. (1968). Manual of Histological Staining Methods of the Armed Forces Institute of Pathology, 3rd edn. New York: McGraw-Hill.
  28. Montes, L. F. & Wilborn, W. H. ( 1968; ). Ultrastructural features of host-parasite relationship in oral candidiasis. J Bacteriol 96, 1349-1356.
    [Google Scholar]
  29. Mukherjee, P. K. & Ghannoum, M. A. ( 2001; ). Secretory proteins in fungal virulence. In Fungal Pathogenesis: Principles and Clinical Applications , pp. 51-79. Edited by R. A. Calderone & R. L. Cihlar. New York:Marcel Dekker.
  30. Odds, F. C. ( 1994; ). Candida albicans, the life and times of a pathogenic yeast. J Med Vet Mycol 32, 1-8.
    [Google Scholar]
  31. Odom, R. B. ( 1994; ). Common superficial fungal infections in immunocompromised patients. J Am Acad Dermatol 31, S56-S59.[CrossRef]
    [Google Scholar]
  32. Pagano, L., Antinori, A., Ammassari, A. & 11 other authors ( 1999; ). Retrospective study of candidemia in patients with hematological malignancies. Clinical features, risk factors and outcome of 76 episodes. Eur J Haematol 63, 77–85.
    [Google Scholar]
  33. Patterson, T. & Andriole, V. T. ( 1989; ). The role of liposomal amphotericin B in the treatment of systemic fungal infections. Eur J Clin Microbiol 25, S63.
    [Google Scholar]
  34. Pope, L. M., Cole, G. T., Guentzel, M. N. & Berry, L. J. ( 1979; ). Systemic and gastrointestinal candidiasis of infant mice after intragastric challenge. Infect Immun 25, 702-707.
    [Google Scholar]
  35. Pugh, D. & Cawson, R. A. ( 1977; ). The cytochemical localization of phospholipase in Candida albicans infecting the chick chorio-allantoic membrane. Sabouraudia 15, 29-35.[CrossRef]
    [Google Scholar]
  36. Ravdin, J. I., Murphy, C. F., Guerrant, R. L. & Long-Krug, S. A. ( 1985; ). Effect of antagonists of calcium and phospholipase A on the cytopathogenicity of Entamoeba histolytica. J Infect Dis 152, 542-549.[CrossRef]
    [Google Scholar]
  37. Rose, M. D., Winston, F. & Hieter, P. (1990). Methods in Yeast Genetics: a Laboratory Course Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  38. Saffer, L. D. & Schwartzman, J. D. ( 1991; ). A soluble phospholipase of Toxoplasma gondii associated with host cell penetration. J Protozool 38, 454-460.[CrossRef]
    [Google Scholar]
  39. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  40. Scherwitz, C. ( 1982; ). Ultrastructure of human cutaneous candidosis. J Investig Dermatol 78, 200-205.[CrossRef]
    [Google Scholar]
  41. Schmiel, D. H. & Miller, V. L. ( 1999; ). Bacterial phospholipases and pathogenesis. Microbes Infect 1, 1103-1112.[CrossRef]
    [Google Scholar]
  42. Seshan, K. R. & Cole, G. T. ( 1994; ). Structural studies of Coccidioides immitis. In Molecular Biology of Pathogenic Fungi , pp. 265-273. Edited by B. Maresca & G. S. Kobayashi. New York:Telos Press.
  43. Silverman, D. J., Santucci, L. A., Meyers, N. & Sekeyova, Z. ( 1992; ). Penetration of hosts by Rickettsia rickettsii appears to be mediated by a phospholipase of rickettsial origin. Infect Immun 60, 2733-2740.
    [Google Scholar]
  44. Spurr, A. R. ( 1969; ). A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res 226, 31-43.
    [Google Scholar]
  45. Sugiyama, Y., Nakashima, S., Mirbod, F., Kanoh, H., Kitajima, Y., Ghannoum, M. A. & Nozawa, Y. ( 1999; ). Molecular cloning of a second phospholipase B gene, caPLB2 from Candida albicans. Med Mycol 37, 61-67.
    [Google Scholar]
  46. Viola, A. M., Lodi, T. & Ferrero, I. ( 1999; ). A Klaac null mutant of Kluyveromyces lactis is complemented by a single copy of the Saccharomyces cerevisiae AAC1 gene. Curr Genet 36, 29-36.[CrossRef]
    [Google Scholar]
  47. Viscoli, C., Girmenia, C., Marinus, A. & 9 other authors ( 1999; ). Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 28, 1071–1079.[CrossRef]
    [Google Scholar]
  48. Wey, S. B., Mori, M., Pfaller, M. A., Woolson, R. F. & Wenzel, R. P. ( 1988; ). Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med 148, 2642-2645.[CrossRef]
    [Google Scholar]
  49. Wey, S. B., Mori, M., Pfaller, M. A., Woolson, R. F. & Wenzel, R. P. ( 1989; ). Risk factors for hospital-acquired candidemia. A matched case-control study. Arch Intern Med 149, 2349-2353.[CrossRef]
    [Google Scholar]
  50. Zhou, D., Chen, L. M., Hernandez, L., Shears, S. B. & Galan, J. E. ( 2001; ). A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol Microbiol 39, 248-259.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-147-9-2585
Loading
/content/journal/micro/10.1099/00221287-147-9-2585
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error