Project/Area Number |
01480176
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
細菌学
|
Research Institution | Yamanashi Medical College |
Principal Investigator |
FUKAZAWA Yoshimura Professor, Department of Microbiology, Yamanashi Medical College, 医学部, 教授 (10087760)
|
Co-Investigator(Kenkyū-buntansha) |
ARAI Tadashi President, Biotherapy Research Association, 会長
MIYAKAWA Yozo Research Associate, Department of Microbiology, Yamanashi Medical College, 医学部, 助手 (00166125)
KAGAYA Keiko Research Associate, Department of Microbiology, Yamanashi Medical College, 医科部, 助手 (60112984)
|
Project Period (FY) |
1989 – 1990
|
Project Status |
Completed (Fiscal Year 1990)
|
Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1990: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1989: ¥3,200,000 (Direct Cost: ¥3,200,000)
|
Keywords | Candida albicans / Catalase / Intracellular killing / Adherence / Mannan / Ergosterol / Dimorphism / Antifungal agents / アゾ-ル系抗真菌剤 |
Research Abstract |
We studied the biological and immunological aspects of pathogenic factors of Candida albicans, a main pathogen for candidiasis. First, we investigated the involvement of catalase in pathogenic factors of the intracellular parasitism of C. albicans. Although catalase production in C. albicans increased by H_2O_2 stimulation, no increase in resistance to killing by neutrophils was observed in the H_2O_2-stimulated yeast cells, indicating that stress-induced catalasre is not a factor of the intracellular parasitism of C. albicans. Second, we determined the nature of adhesin which is required for adherence of C. albicans to host epitherial cells. Adherence ability of antigen mutants defective in C. albicans serotype A-specific antigen (antigen 6) to epitherial cells markedly reduced as compared with their parent and reverlants. ^1H-nuclear magnetic resonance spectral analyses of the purified mannans from the parent and the mutants, and fractionation of their acetolyzed products revealed that
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the mutant mannan lost mannohexaose (M6) with terminal beta-linkage. The fact that the M6 inhibited the agglutination of C. albicans with antigen 6-specific monoclonal antibody showed the significance of M6 as the determinant for antigen 6. These results suggest that the side chains of M6 specific for C. albicans (A) mannan are largely involved in the adherence mechanisms as ligands. Moreover, such finding was supported finding was supported further by the evidence that adherence ability of antigen 6-possessing Candida species (i. e. C.tropicalis) was higher than that of antigen 6-nonpossessing species (i. e. C. guilliermondii.) Finally, we investigated the biochemical mechanisms for dimorphism of C. albicans. To determine the mechanism of inhibition of dimorphism, effect of inhibition of various steps in the pathway for ergosterol biosynthesis on dimorphism were examined by several antifungal agents. As a results, it is suggested that inhibition of dimorphism is related to the loss of ergosterol in cytoplasmic membrane. Less
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