Abstract
The increased prevalence and the severity of oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients are attributed exclusively to the virus-induced immune deficiency of the host. The present study was aimed at answering the question of whether Candida albicans secretory proteinase, a putative virulence factor of the opportunistic C. albicans yeast, has any potential influence on the clinical manifestation of oropharyngeal candidiasis in HIV-positive patients. We measured the secretory proteinase activities of clinical C. albicans isolates from the oropharynges of either HIV-positive individuals (n = 100) or a control group (n = 122). The mean secretory proteinase activity of C. albicans isolates from the HIV-positive group (4,255 +/- 2,372 U/liter) was significantly higher compared with that of isolates from the control group (2,324 +/- 1,487 U/liter) (P < 0.05). The higher level of secretory proteinase activity in the culture supernatants of individual C. albicans isolates correlated with the increased level of proteinase expression on the cell surface, as revealed by cytofluorometry, and with higher levels of secretion of the immunodetectable protein, as shown by Western blotting (immunoblotting). Proteinase activity within the population of C. albicans isolates from HIV-positive individuals was independent of the patient's clinical disease stage and the CD4+/CD8+ cell numbers. Furthermore, no correlation of the proteinase activities with the C. albicans serotype was found, although C. albicans serotype B was significantly more frequent in the HIV-positive group (40%) compared with that in the control group (12%). However, a positive correlation of proteinase activity to antifungal susceptibility was evident.(ABSTRACT TRUNCATED AT 250 WORDS)
Full Text
The Full Text of this article is available as a PDF (312.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Borg-von Zepelin M., Grüness V. Characterization of two monoclonal antibodies against secretory proteinase of Candida tropicalis DSM 4238. J Med Vet Mycol. 1993;31(1):1–15. [PubMed] [Google Scholar]
- Borg M., Rüchel R. Expression of extracellular acid proteinase by proteolytic Candida spp. during experimental infection of oral mucosa. Infect Immun. 1988 Mar;56(3):626–631. doi: 10.1128/iai.56.3.626-631.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Borg M., Watters D., Reich B., Rüchel R. Production and characterization of monoclonal antibodies against secretory proteinase of Candida albicans CBS 2730. Zentralbl Bakteriol Mikrobiol Hyg A. 1988 Mar;268(1):62–73. doi: 10.1016/s0176-6724(88)80116-0. [DOI] [PubMed] [Google Scholar]
- Bouchara J. P., Tronchin G., Annaix V., Robert R., Senet J. M. Laminin receptors on Candida albicans germ tubes. Infect Immun. 1990 Jan;58(1):48–54. doi: 10.1128/iai.58.1.48-54.1990. [DOI] [PMC free article] [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., Linehan L., Wadsworth E., Sandberg A. L. Identification of C3d receptors on Candida albicans. Infect Immun. 1988 Jan;56(1):252–258. doi: 10.1128/iai.56.1.252-258.1988. [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]
- Chandler F. W. Pathology of the mycoses in patients with the acquired immunodeficiency syndrome (AIDS). Curr Top Med Mycol. 1985;1:1–23. doi: 10.1007/978-1-4613-9547-8_1. [DOI] [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]
- Georgopapadakou N. H., Walsh T. J. Human mycoses: drugs and targets for emerging pathogens. Science. 1994 Apr 15;264(5157):371–373. doi: 10.1126/science.8153622. [DOI] [PubMed] [Google Scholar]
- Gustafson K. S., Vercellotti G. M., Bendel C. M., Hostetter M. K. Molecular mimicry in Candida albicans. Role of an integrin analogue in adhesion of the yeast to human endothelium. J Clin Invest. 1991 Jun;87(6):1896–1902. doi: 10.1172/JCI115214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HASENCLEVER H. F., MITCHELL W. O. Antigenic studies of Candida. I. Observation of two antigenic groups in Candida albicans. J Bacteriol. 1961 Oct;82:570–573. doi: 10.1128/jb.82.4.570-573.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heidenreich F., Dierich M. P. Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b. Infect Immun. 1985 Nov;50(2):598–600. doi: 10.1128/iai.50.2.598-600.1985. [DOI] [PMC free article] [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]
- Korting H. C., Ollert M., Georgii A., Fröschl M. In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus. J Clin Microbiol. 1988 Dec;26(12):2626–2631. doi: 10.1128/jcm.26.12.2626-2631.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lanoë J., Dunnigan J. Improvements of the Anson assay for measuring proteolytic activities in acidic pH range. Anal Biochem. 1978 Sep;89(2):461–471. doi: 10.1016/0003-2697(78)90375-5. [DOI] [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]
- Millon L., Manteaux A., Reboux G., Drobacheff C., Monod M., Barale T., Michel-Briand Y. Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype. J Clin Microbiol. 1994 Apr;32(4):1115–1118. doi: 10.1128/jcm.32.4.1115-1118.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyasaki S. H., Hicks J. B., Greenspan D., Polacheck I., MacPhail L. A., White T. C., Agabian N., Greenspan J. S. The identification and tracking of Candida albicans isolates from oral lesions in HIV-seropositive individuals. J Acquir Immune Defic Syndr. 1992 Oct;5(10):1039–1046. [PubMed] [Google Scholar]
- Miyasaki S. H., White T. C., Agabian N. A fourth secreted aspartyl proteinase gene (SAP4) and a CARE2 repetitive element are located upstream of the SAP1 gene in Candida albicans. J Bacteriol. 1994 Mar;176(6):1702–1710. doi: 10.1128/jb.176.6.1702-1710.1994. [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]
- Morrow B., Srikantha T., Anderson J., Soll D. R. Coordinate regulation of two opaque-phase-specific genes during white-opaque switching in Candida albicans. Infect Immun. 1993 May;61(5):1823–1828. doi: 10.1128/iai.61.5.1823-1828.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Odds F. C. Candida albicans proteinase as a virulence factor in the pathogenesis of Candida infections. Zentralbl Bakteriol Mikrobiol Hyg A. 1985 Dec;260(4):539–542. doi: 10.1016/s0176-6724(85)80069-9. [DOI] [PubMed] [Google Scholar]
- Odds F. C. Resistance of yeasts to azole-derivative antifungals. J Antimicrob Chemother. 1993 Apr;31(4):463–471. doi: 10.1093/jac/31.4.463. [DOI] [PubMed] [Google Scholar]
- Ollert M. W., Calderone R. A. A monoclonal antibody that defines a surface antigen on Candida albicans hyphae cross-reacts with yeast cell protoplasts. Infect Immun. 1990 Mar;58(3):625–631. doi: 10.1128/iai.58.3.625-631.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ollert M. W., Frade R., Fiandino A., Panneerselvam M., Petrella E. C., Barel M., Pangburn M. K., Bredehorst R., Vogel C. W. C3-cleaving membrane proteinase. A new complement regulatory protein of human melanoma cells. J Immunol. 1990 May 15;144(10):3862–3867. [PubMed] [Google Scholar]
- Ollert M. W., Söhnchen R., Korting H. C., Ollert U., Bräutigam S., Bräutigam W. Mechanisms of adherence of Candida albicans to cultured human epidermal keratinocytes. Infect Immun. 1993 Nov;61(11):4560–4568. doi: 10.1128/iai.61.11.4560-4568.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ollert M. W., Wadsworth E., Calderone R. A. Reduced expression of the functionally active complement receptor for iC3b but not for C3d on an avirulent mutant of Candida albicans. Infect Immun. 1990 Apr;58(4):909–913. doi: 10.1128/iai.58.4.909-913.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Powderly W. G., Robinson K., Keath E. J. Molecular typing of candida albicans isolated from oral lesions of HIV-infected individuals. AIDS. 1992 Jan;6(1):81–84. doi: 10.1097/00002030-199201000-00010. [DOI] [PubMed] [Google Scholar]
- Pujol C., Reynes J., Renaud F., Raymond M., Tibayrenc M., Ayala F. J., Janbon F., Mallié M., Bastide J. M. The yeast Candida albicans has a clonal mode of reproduction in a population of infected human immunodeficiency virus-positive patients. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9456–9459. doi: 10.1073/pnas.90.20.9456. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ray T. L., Digre K. B., Payne C. D. Adherence of Candida species to human epidermal corneocytes and buccal mucosal cells: correlation with cutaneous pathogenicity. J Invest Dermatol. 1984 Jul;83(1):37–41. doi: 10.1111/1523-1747.ep12261661. [DOI] [PubMed] [Google Scholar]
- Ray T. L., Payne C. D. Comparative production and rapid purification of Candida acid proteinase from protein-supplemented cultures. Infect Immun. 1990 Feb;58(2):508–514. doi: 10.1128/iai.58.2.508-514.1990. [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]
- Remold H., Fasold H., Staib F. Purification and characterization of a proteolytic enzyme from Candida albicans. Biochim Biophys Acta. 1968 Oct 8;167(2):399–406. doi: 10.1016/0005-2744(68)90219-2. [DOI] [PubMed] [Google Scholar]
- Rüchel R., Böning B., Borg M. Characterization of a secretory proteinase of Candida parapsilosis and evidence for the absence of the enzyme during infection in vitro. Infect Immun. 1986 Aug;53(2):411–419. doi: 10.1128/iai.53.2.411-419.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rüchel R., Ritter B., Schaffrinski M. Modulation of experimental systemic murine candidosis by intravenous pepstatin. Zentralbl Bakteriol. 1990 Aug;273(3):391–403. doi: 10.1016/s0934-8840(11)80443-3. [DOI] [PubMed] [Google Scholar]
- Samaranayake L. P., Holmstrup P. Oral candidiasis and human immunodeficiency virus infection. J Oral Pathol Med. 1989 Dec;18(10):554–564. doi: 10.1111/j.1600-0714.1989.tb01552.x. [DOI] [PubMed] [Google Scholar]
- Sanguineti A., Carmichael J. K., Campbell K. Fluconazole-resistant Candida albicans after long-term suppressive therapy. Arch Intern Med. 1993 May 10;153(9):1122–1124. [PubMed] [Google Scholar]
- Schmid J., Odds F. C., Wiselka M. J., Nicholson K. G., Soll D. R. Genetic similarity and maintenance of Candida albicans strains from a group of AIDS patients, demonstrated by DNA fingerprinting. J Clin Microbiol. 1992 Apr;30(4):935–941. doi: 10.1128/jcm.30.4.935-941.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smail E. H., Jones J. M. Demonstration and solubilization of antigens expressed primarily on the surfaces of Candida albicans germ tubes. Infect Immun. 1984 Jul;45(1):74–81. doi: 10.1128/iai.45.1.74-81.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Torssander J., Morfeldt-Månson L., Biberfeld G., Karlsson A., Putkonen P. O., Wasserman J. Oral candida albicans in HIV infection. Scand J Infect Dis. 1987;19(3):291–295. doi: 10.3109/00365548709018473. [DOI] [PubMed] [Google Scholar]
- Whelan W. L., Kirsch D. R., Kwon-Chung K. J., Wahl S. M., Smith P. D. Candida albicans in patients with the acquired immunodeficiency syndrome: absence of a novel of hypervirulent strain. J Infect Dis. 1990 Aug;162(2):513–518. doi: 10.1093/infdis/162.2.513. [DOI] [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]
- el-Maghrabi E. A., Dixon D. M., Burnett J. W. Characterization of Candida albicans epidermolytic proteases and their role in yeast-cell adherence to keratinocytes. Clin Exp Dermatol. 1990 May;15(3):183–191. doi: 10.1111/j.1365-2230.1990.tb02069.x. [DOI] [PubMed] [Google Scholar]