Abstract
Several strains of Candida albicans were compared for their ability to cause vaginal infection in a rat model, and their vaginopathic potentials were correlated with the expression of two aspartyl proteinases genes (SAP1 and SAP2) and adherence in vivo to the vaginal epithelium. Dot blot reactions and Northern blot analysis with RNA extracted from the vaginal fluid of rats infected with the highly vaginopathic strains H12 and 10261 demonstrated the expression of both SAP1 and SAP2 during the first week of infection. In contrast, neither gene was expressed during infection by a nonvaginopathic strain (N), even though the organism could be recovered during the first 24 h postinfection. A moderately vaginopathic strain (P) also expressed both genes, but the level of SAP1 mRNA appeared to decrease prior to that of SAP2. Neither gene was expressed, even by the highly vaginopathic strains, after the first week of infection, concomitant with a decrease in the number of organisms recovered from the vaginas. Analysis of in vivo adherence showed that the nonvaginopathic strain (N) adhered to vaginal epithelial cells less readily than the highly vaginopathic strain (H12) and moderately vaginopathic strain (P). Thus, in addition to its inability to express SAP1 and SAP2 in vivo, the nonvaginopathic strain does not colonize host cells to the same extent as the other strains tested. Our results demonstrate the early in vivo expression of two aspartyl proteinase gene during candidal vaginitis and suggest its association with the establishment of a vaginal infection.
Full Text
The Full Text of this article is available as a PDF (414.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Borg M., Rüchel R. Demonstration of fungal proteinase during phagocytosis of Candida albicans and Candida tropicalis. J Med Vet Mycol. 1990;28(1):3–14. [PubMed] [Google Scholar]
- Brawner D. L., Cutler J. E. Oral Candida albicans isolates from nonhospitalized normal carriers, immunocompetent hospitalized patients, and immunocompromised patients with or without acquired immunodeficiency syndrome. J Clin Microbiol. 1989 Jun;27(6):1335–1341. doi: 10.1128/jcm.27.6.1335-1341.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Calderone R. A., Braun P. C. Adherence and receptor relationships of Candida albicans. Microbiol Rev. 1991 Mar;55(1):1–20. doi: 10.1128/mr.55.1.1-20.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantorna M. T., Balish E. Mucosal and systemic candidiasis in congenitally immunodeficient mice. Infect Immun. 1990 Apr;58(4):1093–1100. doi: 10.1128/iai.58.4.1093-1100.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cassone A., De Bernardis F., Mondello F., Ceddia T., Agatensi L. Evidence for a correlation between proteinase secretion and vulvovaginal candidosis. J Infect Dis. 1987 Nov;156(5):777–783. doi: 10.1093/infdis/156.5.777. [DOI] [PubMed] [Google Scholar]
- 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]
- De Bernardis F., Adriani D., Lorenzini R., Pontieri E., Carruba G., Cassone A. Filamentous growth and elevated vaginopathic potential of a nongerminative variant of Candida albicans expressing low virulence in systemic infection. Infect Immun. 1993 Apr;61(4):1500–1508. doi: 10.1128/iai.61.4.1500-1508.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Bernardis F., Agatensi L., Ross I. K., Emerson G. W., Lorenzini R., Sullivan P. A., Cassone A. Evidence for a role for secreted aspartate proteinase of Candida albicans in vulvovaginal candidiasis. J Infect Dis. 1990 Jun;161(6):1276–1283. doi: 10.1093/infdis/161.6.1276. [DOI] [PubMed] [Google Scholar]
- De Bernardis F., Boccanera M., Rainaldi L., Guerra C. E., Quinti I., Cassone A. The secretion of aspartyl proteinase, a virulence enzyme, by isolates of Candida albicans from the oral cavity of HIV-infected subjects. Eur J Epidemiol. 1992 May;8(3):362–367. doi: 10.1007/BF00158569. [DOI] [PubMed] [Google Scholar]
- De Bernardis F., Lorenzini R., Verticchio R., Agatensi L., Cassone A. Isolation, acid proteinase secretion, and experimental pathogenicity of Candida parapsilosis from outpatients with vaginitis. J Clin Microbiol. 1989 Nov;27(11):2598–2603. doi: 10.1128/jcm.27.11.2598-2603.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Bernardis F., Molinari A., Boccanera M., Stringaro A., Robert R., Senet J. M., Arancia G., Cassone A. Modulation of cell surface-associated mannoprotein antigen expression in experimental candidal vaginitis. Infect Immun. 1994 Feb;62(2):509–519. doi: 10.1128/iai.62.2.509-519.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edison A. M., Manning-Zweerink M. Comparison of the extracellular proteinase activity produced by a low-virulence mutant of Candida albicans and its wild-type parent. Infect Immun. 1988 May;56(5):1388–1390. doi: 10.1128/iai.56.5.1388-1390.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Franzke S., Calderone R. A., Schaller K. Isolation of avirulent clones of Candida albicans with reduced ability to recognize the CR2 ligand C3d. Infect Immun. 1993 Jun;61(6):2662–2669. doi: 10.1128/iai.61.6.2662-2669.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukazawa Y., Cassone A., Bistoni F., Howard D. H., Kagaya K., Murphy J. W., Cenci E., Lane T. E., Mencacci A., Puccetti P. Mechanisms of cell-mediated immunity in fungal infection. J Med Vet Mycol. 1994;32 (Suppl 1):123–131. doi: 10.1080/02681219480000781. [DOI] [PubMed] [Google Scholar]
- Ganesan K., Banerjee A., Datta A. Molecular cloning of the secretory acid proteinase gene from Candida albicans and its use as a species-specific probe. Infect Immun. 1991 Sep;59(9):2972–2977. doi: 10.1128/iai.59.9.2972-2977.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Germaine G. R., Tellefson L. M. Effect of pH and human saliva on protease production by Candida albicans. Infect Immun. 1981 Jan;31(1):323–326. doi: 10.1128/iai.31.1.323-326.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ghannoum M., Abu Elteen K. Correlative relationship between proteinase production, adherence and pathogenicity of various strains of Candida albicans. J Med Vet Mycol. 1986 Oct;24(5):407–413. doi: 10.1080/02681218680000621. [DOI] [PubMed] [Google Scholar]
- Holmberg K., Meyer R. D. Fungal infections in patients with AIDS and AIDS-related complex. Scand J Infect Dis. 1986;18(3):179–192. doi: 10.3109/00365548609032326. [DOI] [PubMed] [Google Scholar]
- Hube B., Turver C. J., Odds F. C., Eiffert H., Boulnois G. J., Köchel H., Rüchel R. Sequence of the Candida albicans gene encoding the secretory aspartate proteinase. J Med Vet Mycol. 1991;29(2):129–132. [PubMed] [Google Scholar]
- Imam N., Carpenter C. C., Mayer K. H., Fisher A., Stein M., Danforth S. B. Hierarchical pattern of mucosal candida infections in HIV-seropositive women. Am J Med. 1990 Aug;89(2):142–146. doi: 10.1016/0002-9343(90)90291-k. [DOI] [PubMed] [Google Scholar]
- Klein R. S., Harris C. A., Small C. B., Moll B., Lesser M., Friedland G. H. Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N Engl J Med. 1984 Aug 9;311(6):354–358. doi: 10.1056/NEJM198408093110602. [DOI] [PubMed] [Google Scholar]
- Kwon-Chung K. J., Lehman D., Good C., Magee P. T. Genetic evidence for role of extracellular proteinase in virulence of Candida albicans. Infect Immun. 1985 Sep;49(3):571–575. doi: 10.1128/iai.49.3.571-575.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magee B. B., Hube B., Wright R. J., Sullivan P. J., Magee P. T. The genes encoding the secreted aspartyl proteinases of Candida albicans constitute a family with at least three members. Infect Immun. 1993 Aug;61(8):3240–3243. doi: 10.1128/iai.61.8.3240-3243.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Monod M., Togni G., Hube B., Sanglard D. Multiplicity of genes encoding secreted aspartic proteinases in Candida species. Mol Microbiol. 1994 Jul;13(2):357–368. doi: 10.1111/j.1365-2958.1994.tb00429.x. [DOI] [PubMed] [Google Scholar]
- Morrison C. J., Hurst S. F., Bragg S. L., Kuykendall R. J., Diaz H., Pohl J., Reiss E. Heterogeneity of the purified extracellular aspartyl proteinase from Candida albicans: characterization with monoclonal antibodies and N-terminal amino acid sequence analysis. Infect Immun. 1993 May;61(5):2030–2036. doi: 10.1128/iai.61.5.2030-2036.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrow B., Srikantha T., Soll D. R. Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans. Mol Cell Biol. 1992 Jul;12(7):2997–3005. doi: 10.1128/mcb.12.7.2997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ray T. L., Payne C. D. Scanning electron microscopy of epidermal adherence and cavitation in murine candidiasis: a role for Candida acid proteinase. Infect Immun. 1988 Aug;56(8):1942–1949. doi: 10.1128/iai.56.8.1942-1949.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani L., Mocci S., Bietta C., Lanfaloni L., Puccetti P., Bistoni F. Th1 and Th2 cytokine secretion patterns in murine candidiasis: association of Th1 responses with acquired resistance. Infect Immun. 1991 Dec;59(12):4647–4654. doi: 10.1128/iai.59.12.4647-4654.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross I. K., De Bernardis F., Emerson G. W., Cassone A., Sullivan P. A. The secreted aspartate proteinase of Candida albicans: physiology of secretion and virulence of a proteinase-deficient mutant. J Gen Microbiol. 1990 Apr;136(4):687–694. doi: 10.1099/00221287-136-4-687. [DOI] [PubMed] [Google Scholar]
- Rüchel R. Cleavage of immunoglobulins by pathogenic yeasts of the genus Candida. Microbiol Sci. 1986 Oct;3(10):316–319. [PubMed] [Google Scholar]
- Rüchel R., Zimmermann F., Böning-Stutzer B., Helmchen U. Candidiasis visualised by proteinase-directed immunofluorescence. Virchows Arch A Pathol Anat Histopathol. 1991;419(3):199–202. doi: 10.1007/BF01626348. [DOI] [PubMed] [Google Scholar]
- Rüchel R., de Bernardis F., Ray T. L., Sullivan P. A., Cole G. T. Candida acid proteinases. J Med Vet Mycol. 1992;30 (Suppl 1):123–132. [PubMed] [Google Scholar]
- Samaranayake Y. H., MacFarlane T. W., Samaranayake L. P., Aitchison T. The in vitro proteolytic and saccharolytic activity of Candida species cultured in human saliva. Oral Microbiol Immunol. 1994 Aug;9(4):229–235. doi: 10.1111/j.1399-302x.1994.tb00063.x. [DOI] [PubMed] [Google Scholar]
- Shimizu K., Kondoh Y., Tanaka K. Proteinase production and pathogenicity of Candida albicans. I. Invasion into chorioallantoic membrane by C. albicans strains of different proteinase activity. Microbiol Immunol. 1987;31(11):1045–1060. doi: 10.1111/j.1348-0421.1987.tb01337.x. [DOI] [PubMed] [Google Scholar]
- Sobel J. D. Pathogenesis of Candida vulvovaginitis. Curr Top Med Mycol. 1989;3:86–108. doi: 10.1007/978-1-4612-3624-5_5. [DOI] [PubMed] [Google Scholar]
- Soll D. R. High-frequency switching in Candida albicans. Clin Microbiol Rev. 1992 Apr;5(2):183–203. doi: 10.1128/cmr.5.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White T. C., Miyasaki S. H., Agabian N. Three distinct secreted aspartyl proteinases in Candida albicans. J Bacteriol. 1993 Oct;175(19):6126–6133. doi: 10.1128/jb.175.19.6126-6133.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright R. J., Carne A., Hieber A. D., Lamont I. L., Emerson G. W., Sullivan P. A. A second gene for a secreted aspartate proteinase in Candida albicans. J Bacteriol. 1992 Dec;174(23):7848–7853. doi: 10.1128/jb.174.23.7848-7853.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]