Biochemical and Immunological Studies on Pathogenic Factors of Candida Albicans

白色念珠菌致病因素的生化和免疫学研究

• 批准号: 01480176
• 负责人: FUKAZAWA Yoshimura
• 金额: $ 3.52万
• 依托单位: Yamanashi Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480176/
• 关键词: Candida albicans; Catalase; Intracellular killing; Adherence; Mannan; Ergosterol; Dimorphism; Antifungal agents; アゾ-ル系抗真菌剤

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 … More 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

本文从生物学和免疫学的角度研究了白色念珠菌的致病因子，首先探讨了过氧化氢酶在白念珠菌胞内寄生致病因子中的作用。虽然过氧化氢促进白念珠菌产生过氧化氢酶，但在H_2O_2刺激的酵母细胞中，对中性粒细胞杀伤的抵抗力没有增加，这表明应激诱导的过氧化氢酶不是白念珠菌细胞内寄生的一个因素。其次，我们确定了白念珠菌与宿主上皮细胞黏附所需的粘附素的性质。白念珠菌A型特异性抗原(6号抗原)缺陷突变株对上皮细胞的黏附能力明显低于亲本和突变株。亲本和突变体纯化的甘露聚糖的~1H-核磁共振波谱分析和乙酰化产物的分级分析表明，…此外，突变的甘露聚糖(M6)失去了末端的β-键。M6能抑制白念珠菌与抗原6特异性的单抗的凝集，表明M6作为抗原6的决定簇具有重要意义。这些结果表明，白念珠菌甘露聚糖特异性的M6侧链作为配体参与了黏附机制。此外，有证据表明，具有抗原6的念珠菌(即热带念珠菌)的黏附能力高于不具有抗原6的念珠菌(即Guilliermondii)，这进一步支持了这一发现。最后，我们探讨了白色念珠菌二型性的生化机制。为了探讨麦角甾醇生物合成途径抑制二形性的机制，用几种抗真菌药物研究了抑制麦角甾醇生物合成途径中各个步骤对二形性的影响。结果表明，抑制二态现象与细胞膜中麦角甾醇的丢失有关。较少

项目成果

宮川 洋三: "カンジダ表層抗原と病原性因子" 細胞. 22. 58-62 (1990)

Yozo Miyakawa：“念珠菌表面抗原和毒力因子”细胞。22. 58-62 (1990)

Y.MIYAKAWA: "Isolation and Chemical and Biological Characterization of Antigenic Mutants of Candida albicans Serotype A" Yeast. 5. 225-229 (1989)

Y.MIYAKAWA：“白色念珠菌 A 血清型”酵母抗原突变体的分离及其化学和生物学特征。

T.Kuribayashi: "Comparative study of Candida adherence to various cell lines of human epitherium" Infection and Immunity.

T.Kuribayashi：“念珠菌粘附于人上皮各种细胞系的比较研究”感染和免疫。

Y. Miyakawa,: "Role of cell surface antigen in Candida infection" The cell. 22. 58-62 (1990)

Y. Miyakawa，：“细胞表面抗原在念珠菌感染中的作用”细胞。

Y.Miyakawa: "Isolation and chemical biological characterization of antigenic mutants of Candida albicans serotype A" Yeast. 5. 225-229 (1989)

Y.Miyakawa：“白色念珠菌 A 血清型抗原突变体的分离和化学生物学特性”酵母。