FUNGAL PROTEIN/GLYCOPROTEIN EXPRESSION IN TINEA CAPITIS

头癣中真菌蛋白/糖蛋白的表达

• 批准号: 6259345
• 负责人: SUSAN M ABDEL-RAHMAN
• 金额: $ 6.18万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6259345
• 关键词: African American; adolescence (12-20); child (0-11); clinical research; communicable disease transmission; endopeptidases; enzyme activity; epitope mapping; fluorescent dye /probe; fungal antigens; fungal proteins; gene expression; genetic strain; glycoproteins; host organism interaction; human subject; microorganism growth; pathologic process; polymerase chain reaction; statistics /biometry; tinea; virulence

Worldwide, tinea capitis remains a persistent and highly infection in children with as many as 1 in 10 children at any ne time demonstrating active infection or serving as carriers of the fungus. At the applicant institution we treated 4.5 children per day in 1999. Although tinea capitis is not life threatening, it is a major pediatric health concern for a number of reasons: 1) the causative organisms are communicable and non- opportunistic, 2) the infection does not adequately respond to topical therapy requiring systemic antifungal treatment for months to years, 3) concerns regarding appearance and spread of infection lead to the exclusion of children from participation in academic and social activities and 4) psychological concerns surround those children who develop permanent alopecia as a result of infection. Moreover, the cost of health care systems from clinic visits, drug failure, adverse events, drug interactions, non-compliance, drug acquisition and monitoring costs and associated morbidity present an overwhelming problem in pediatric medicine. Despite the fact that tinea capitis was described over a century ago, the rate of infection continues to grow and little remains known regarding the factors involved in the pathogenesis of this disease. For example, it is unclear why a single species of fungus is capable of resulting in vastly divergent clinical presentations including an asymptomatic carrier state, a chronic non-inflammatory disease state and an acute severely-inflammatory disease state. It is likely that both host and fungal factors are involved in a complex interaction that defines disease progression in the human host. We hypothesize that strain- specific variability in the balance between antigenic protease expression and immunoinhibitory glycoprotein production dictates the variability in the response seen between different children with tinea capitis. This study is designed to determine whether strain specific differences exist in (1) the type of fungal proteases liberated, (2) the extent of fungal proteases activity and (3) the type of fungal glycoproteins produced for fungal isolates collected from children with inflammatory and non-inflammatory disease. Identification of a correlation between fungal protein/glycoprotein expression and the severity of clinical disease will more clearly define the role of these factors in disease pathogenesis. Successful characterization of these fungal elements is the first step toward developing potential treatment that targets critical steps in fungal intermediary metabolism and is critical for the isolation of fungal epitopes sufficient to evoke an immune response that can subsequently serve as the basis for the development of a vaccine sufficient to prevent infection.

在世界范围内，头皮炎仍然是儿童的持续和高度感染，任何时候都有多达1/10的儿童表现出活动性感染或作为真菌的携带者。1999年，我们在申请机构每天治疗4.5名儿童。虽然头皮炎不会危及生命，但它是一个主要的儿科健康问题，原因如下：1）致病微生物是传染性的和非机会性的，2）感染对局部治疗没有充分的反应，需要数月至数年的全身抗真菌治疗，3）对感染的出现和传播的担忧导致儿童被排除在学术和社会活动之外，以及4）那些由于感染而患上永久性脱发症的儿童会受到心理上的关注。此外，来自诊所就诊、药物失败、不良事件、药物相互作用、不依从性、药物获取和监测成本以及相关发病率的医疗保健系统的成本在儿科医学中呈现出压倒性的问题。尽管在世纪前就描述了头骨炎，但感染率仍在继续增长，关于这种疾病的发病机制所涉及的因素仍然知之甚少。例如，目前尚不清楚为什么单一种真菌能够导致截然不同的临床表现，包括无症状的携带者状态、慢性非炎性疾病状态和急性非炎性疾病状态。很可能宿主和真菌因素都参与了定义人类宿主疾病进展的复杂相互作用。我们假设，抗原蛋白酶表达和免疫抑制糖蛋白产生之间平衡的菌株特异性变异决定了不同小头症儿童之间反应的变异性。本研究旨在确定菌株特异性差异是否存在于（1）释放的真菌蛋白酶的类型，（2）真菌蛋白酶活性的程度和（3）从患有炎症和非炎症疾病的儿童中收集的真菌分离株产生的真菌糖蛋白的类型。鉴定真菌蛋白/糖蛋白表达与临床疾病严重程度之间的相关性将更清楚地定义这些因素在疾病发病机制中的作用。这些真菌元件的成功表征是开发针对真菌中间代谢中的关键步骤的潜在治疗的第一步，并且对于足以引起免疫应答的真菌表位的分离是至关重要的，所述免疫应答随后可以用作开发足以预防感染的疫苗的基础。