Abstract
Researches on Candidal heat-shock protein 90 (HSP90) in recent years are summarized.Candida albicans is a commensal pathogen in human and animals. In immunocompromised individuals it behaves as an opportunist pathogen, giving rise to superficial or systemic infections. Systemic candidosis is a common cause of death among immunocompromised and debilitated patients, in which the mortality is as high as 70%. HSP90 is now recognized as an immunodominant antigen inC. albicans and plays a key role in systemic candidosis as a molecular chaperone. The 47-ku peptide is the breakdown product of HSP90. Patients who has recovered from systemic candidosis produce high titre of antibodies to 47-ku antigen, whereas the fatal cases have little antibody or falling titres. The three commonest epitopes of candidal HSP90 have been mapped, epitopes C, B and H. Epitopes C and H are immunogenic. The antibody probes of both epitopes may be developed into a new serological test agents for systemic candidosis due to rather high specificity and sensitivity. The recent results establish HSP90 as an ATP-dependent chaperone that is involved in the folding of cell regulatory proteins and in the refolding of stress-denatured polypeptides. Some researches on fungal HSP90 and the treatment of patients with candidosis are reviewed as well.
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References
O’Connell, B. C., Xu, T., Walsh, T. J. et al., Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands, Hum. Gene. Ther., 1996. 18: 2255.
Matthews, R. C.,Candida albicans HSP 90: link between protective and auto-immunity, J. Med. Microbiol., 1992, 36: 367.
Matthews, R. C., Burnie, J. P., The role of HSP90 in fungal infection, Immunol. Today, 1992, 13(9): 345.
Ellis, J., Proteins as molecular chaperones. Nature, 1987, 328: 378.
Walsh, P., Norris, D. A., Abe, J., Candida albicans induces selective expansion of human T lymphocytes expressing the T-cell receptor variable region V beta 5.1. J. Dermatol. Sci., 1996, 12(2): 140.
Matthews, R., Burnie, J. P., Lee, W., The application of epitope mapping in the development of a new serological test for systemic candidosis. J. Immunol. Methods, 1991, 143: 73.
Matthews, R., Burnie, J., Antibodies against Candida: potential therapeutics? Trends Microbiol., 1996, 4(9): 354.
Matthews, R., Hodgells, S., Burnie, J., Preliminary assessment of a human recombinant antibody fragment to HSP90 in murine invasive candidasis. J. Infect. Dis. 1995, 171(6): 1668.
Matthews, R. C., Burnie, J. P., Howat, D. et al., Autoantibody to heat shock protein 90 can mediate protection against systemic candidosis, Immunology. 1991, 74: 20.
Zhi-zhen, W., The new-peptide chain’s folding and chaperones, in The Advanced Field of Life Sciences Forward 21th Century (in Chinese) (ed. Li, B. J.). Guangdong: Guangzhou Science and Technology Press, 1996, 93.
Obermann, W. M. J., Sondermann, H., Russo, A. A. et al.,In vivo function of HSP90 is dependent on ATP binding and ATP hydrolysis. J. Cell Biol., 1998, 143(4): 901.
Schwartz, J. A., Mizukami, H., A metal-linked gapped zipper model is proposed for the 90KUa heat shock protein-estrogen receptor interface, Med Hypoth., 1991, 35: 140.
Rebbe, N. F., Ware, J., Bertina, R. M. el al., Nucleotide sequence of a cDNA for a member of the human 90-kua heat-shock protein family. Gene, 1987. 53: 235.
Swoboda, R. K., Bertram, G., Budge, S. et al., Structure and regulation of the HSP90 gene from the pathogenic fungusCandida albicans, Infect. Immun., 1995, 63(11): 4506.
Burnie, J. P., Matthews, R. C., Heal shock protein 88 and Aspergillus infection, J. Clin. Microbiol., 1991, 29(10): 2099.
Hodgetts, S., Matthews, R., Morrissey, G. et al., Over-expression ofSaccharomyces cerevisiae HSP90 enhances the virulence of this yeast in mice, FEMS Immunol. Med. Microbiol., 1996, 16(3-4): 229.
Ziegler, E. J., Fisher, C. J., Sorung, C. L. el al., Treatment of gram-negative bacteria and septic shock with HA-IA human monoclonal antibody against endotoxin, New Engl. J. Med., 1991, 324: 429.
Driscoll, J., Duan, C., Zuo, Y. et al., Candidacidal activity of human salivary histatin recombinant variants produced by site-directed mutagenesis. Gene, 1996, 177: 1–2, 29–34.
Tsai, H., Bobek, L. A., Studies of the mechanism of human salivary histatin-5 candidacidal activity with histatin-5 variants and azole-sensitive and resistant Candida species, Antimicrob Agents Chemother, 1997, 41(10): 2224.
Galea-Lauri, J., Richardson, A. J., Latchman, D. S. et al., Increased heat shock protein 90 (HSP90) expression leads to increased apoptosis in the monoblastoid cell line U937 following induction with TNF-alpha and cycioheximide: a possible role in immunopathology. J. Immunol., 1996, 157(9): 4109.
Stahl, M., Ludwig, D., Fellermann, K. et al., Intestinal expression of human heat shock protein 90 in patients with Crohn’s disease and ulcerative colitis. Dig. Dis. Sci., 1998, 43(5): 1079.
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Wang, L., Zhu, X. Heat-shock protein 90 inCandida albicans . Chin.Sci.Bull. 45, 481–484 (2000). https://doi.org/10.1007/BF02887089
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DOI: https://doi.org/10.1007/BF02887089