CANDIDA ACID PROTEINASE AND PATHOGENESIS

念珠菌作为病原体的成功可能在一定程度上取决于高频率 在一般表型及其相关表达之间切换 假定的毒力基因集在复合体中(但不是 特别是)促进和构成了菌株的致病行为。 一种可能的毒力因子，假丝酵母酸性蛋白酶(CAP)，是 通过开关表型的差异表达，促进致病 行为，并且是假设集合中的成员资格的主要候选者 念珠菌的毒力基因。我们问：1)是否有特定的开关表型和 它们的CAP分泌与共生或致病行为相关？2) 患者CAP抗体或抗原的滴度是否与感染有关， 表型和CAP分泌？3)切换表型和CAP分泌 与观察到的和实验中的致病行为有关？该项目将 确定开关表型和CAP是否区分共生和 致病性念珠菌的分离及其与人和实验的相关性 动物感染。 1.共生念珠菌和致病念珠菌CAP分泌量的测定 分离株和表型。共生菌和病原菌及其相互作用 将获得正常人和念珠菌病患者的表型。 每种表型的帽子分泌将被评估并与1) 分离株的共生或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.皮肤粘膜和皮肤粘膜中的帽抗体反应和抗原存在 系统性念珠菌病。系统性红斑狼疮或系统性红斑狼疮患者的血清 念珠菌病，或皮肤黏膜念珠菌病和念珠菌病 殖民主义，将会获得。冠状抗体和抗原将被 采用酶联免疫吸附试验和乳胶凝集试验测定。感染组织将会是 免疫荧光法检测CAP沉淀物。冠状抗原在 血清、组织和CAP抗体滴度将与临床相关 临床表现、患者的隔离和切换表型及其CAP 分泌物。血清CAP抗体和抗原滴度的预测价值 感染的原因将会被确定。CAP的分泌和存在情况 活体可能与感染菌株和转换表型相关。 3.假丝酵母菌的致病力及其转换表型 实验性念珠菌病。共生菌株和致病菌株的毒力 念珠菌感染的转换表型将在小鼠身上进行测试 念珠菌病的模型。毒力将与分离物相关 患者的行为、起源、使用的转换表型和CAP 分泌物。这将演示交换机表型和CAP的作用 将实验性感染的分泌物与临床感染进行比较。 从共生表型到致病表型的转换和 CAP的分泌可能被阐明。

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.