CANDIDA ACID PROTEINASE AND PATHOGENESIS

念珠菌酸性蛋白酶和发病机制

• 批准号: 2062556
• 负责人: THOMAS L RAY
• 金额: $ 16.68万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2062556
• 关键词: Candida; agglutination reaction; antifungal antibody; antigen antibody reaction; candidiasis; endopeptidases; enzyme linked immunosorbent assay; enzyme mechanism; fungal genetics; gene expression; host organism interaction; human subject; immunofluorescence technique; laboratory mouse; laboratory rat; microorganism culture; microorganism immunology; nucleic acid sequence; phenotype; protein biosynthesis; serology /serodiagnosis; virulence

Success of Candida as a pathogen may depend partly on high frequency switching between general phenotypes and their associated expression of hypothetical sets of virulence genes that in the composite (but not singularly) facilitate and constitute a strain's pathogenic behavior. One putative virulence factor, Candida acid proteinase (CAP), is differentially expressed by switch phenotypes, facilitates pathogenic behavior, and is a prime candidate for membership in the hypothetical set of Candida virulence genes. We ask: 1) Do specific switch phenotypes and their CAP secretion correlate with commensal or pathogenic behavior? 2) Do patient titers of CAP antibody or antigen correlate with infection, phenotypes and CAP secretion? 3) Do switch phenotypes and CAP secretion relate to observed and experimental pathogenic behavior? The project will determine if switch phenotypes and CAP discriminate between commensal and pathogenic Candida isolates, and correlate with human and experimental animal infections. 1. Quantitation of CAP Secretion by Commensal and Pathogenic Candida Isolates and Phenotypes. Commensal and pathogenic isolates and their phenotypes from normals and patients with candidiasis, will be obtained. CAP secretion of each phenotype will be assessed and correlated with 1) commensal or pathogenic behavior of isolates and switch phenotypes in patients and 2) the pathogenicity of phenotypes in experimental candidiasis. 2. CAP Antibody Response and Antigenic Presence in Mucocutaneous and Systemic Candidiasis. Sera of patients at risk to or with systemic candidiasis, or with mucocutaneous candidiasis and those with Candida colonization, will be obtained. CAP antibody and antigen will be measured by ELISA and latex agglutination. Tissue of infections will be tested for CAP deposits by immunofluorescent methods. CAP antigen in sera and tissue and CAP antibody titers will be correlated with clinical manifestations, the patient's isolate and switch phenotypes and their CAP secretion. Predictive values of CAP antibody and antigen titers in sera for infections will be determined. The secretion and presence of CAP in vivo with be correlated with infecting strains and switch phenotypes. 3. Pathogenicity of Candida Isolates and Their Switch Phenotypes in Experimental Candidiasis. Virulence of commensal and pathogenic isolates and switch phenotypes from Candida infections will be tested in murine models of candidiasis. Virulence will be correlated with isolate behavior in the patient of, origin, the switch phenotype used, and CAP secretion. This will demonstrate the role of switch phenotypes and CAP secretion in experimental infections to compare with clinical infections. Transitions from commensal to pathogenic phenotypes through switching and CAP secretion may be elucidated.

念珠菌作为病原体的成功可能部分取决于高频率 在一般表型和它们的相关表达之间切换 假设的毒力基因组，在复合材料（但不是 奇异地）促进并构成菌株致病行为。 一种假定的毒力因子是念珠菌酸性蛋白酶（CAP）， 通过转换表型差异表达， 行为，并且是假设集合中成员资格的主要候选者 假丝酵母毒力基因 我们问：1）特定的开关表型和 他们的CAP分泌与行为或致病行为相关吗？（二） 患者CAP抗体或抗原滴度是否与感染相关， 表型和CAP分泌？3)转换表型和CAP分泌 与观察到的和实验性的致病行为有关吗该项目将 确定开关表型和CAP是否能区分BSal和 致病性念珠菌分离株，并与人类和实验 动物感染。 1.常见和致病性念珠菌CAP分泌的定量测定 分离株和表型。共生菌和致病菌及其 将获得来自正常人和念珠菌病患者的表型。 将评估每种表型的CAP分泌，并与1） 分离株的致病行为和转换表型 患者和2）实验中表型的致病性 念珠菌病 2. CAP抗体应答和粘膜皮肤和 全身性寄生虫病 有全身性疾病风险或全身性疾病患者的血清 念珠菌病，或皮肤粘膜念珠菌病和念珠菌病 殖民地，将获得。 CAP抗体和抗原将 通过ELISA和乳胶凝集测定。 感染组织将 通过免疫荧光方法检测CAP沉积物。 CAP抗原 血清和组织以及CAP抗体滴度将与临床 临床表现，患者的分离和转换表型及其CAP 分泌物 血清中CAP抗体和抗原滴度的预测价值 感染将被确定。 CAP的分泌和存在， 体内与感染菌株和转换表型相关。 3.假丝酵母菌致病性及其转换表型研究 实验性寄生虫病。 真菌和致病菌株的毒力 将在小鼠中测试念珠菌感染的转换表型 念珠菌病的模型。 毒力将与分离株相关 患者的行为、起源、使用的开关表型和CAP 分泌物 这将证明开关表型和CAP的作用 实验感染的分泌与临床感染比较。 通过转换和 CAP分泌可以被阐明。