Biology and Drug Resistance of Candida Biofilms

描述（由申请方提供）：与牙列相关的义齿性口炎 （慢性萎缩性念珠菌病）是最普遍的浅表性口腔感染 也是最常见的与疟疾相关的疾病义齿的病因 口腔炎涉及牙菌斑。牙菌斑由复杂的生物膜组成 细菌和酵母菌主要是白色念珠菌C.白色念珠菌生物膜 比细菌生物膜受到的关注要少得多， 对它们的生物学和抗药性的了解还处于初级阶段。 频繁的义齿性口炎治疗失败， 越来越多的老年人，其中许多人将是无齿的，使 这一研究领域尤为重要。我们工作的长远目标是 了解C.白色念珠菌生物膜我们 在这一新领域的初步工作导致成功地开发了一个 C.白色念珠菌相关生物膜（出版物#1）。以来 在上一篇论文中，我们使用这个模型：1）定义了C语言的三个阶段。 白色念珠菌与生物膜形成有关;白色 生物膜是高度异质结构，3）表明抗真菌 C.抗性白色念珠菌生物膜增加与生物膜 4）表明C.白色念珠菌的能力比 致病性C.近平滑和酿酒酵母形成义齿 生物膜; 5）C.白念珠菌基因在不同的 生物膜和缺氧条件。此外，我们还努力 构建一个C.白念珠菌DNA阵列，并开发了一种生物假体相关的 念珠菌生物膜模型重要的是，我们的研究表明，生物膜生长在 我们的体外模型具有与在导管上生长的体内模型相似的形态 从患有导管相关感染的患者获得。具体目标 目前的建议是：具体目标1：使用我们建立的生物膜模型， 测定念珠菌的抗真菌药敏谱。白色念珠菌分离株 从义齿性口炎患者中获得，并研究 抗真菌药物对C.白念珠菌生物膜具体目标 2：研究抗真菌药物增加的机制 生物膜相关的C.白色念珠菌具体目标3：识别基因 它们参与了 C.白色念珠菌生物膜通过研究生物膜模型 系统，并将这些知识应用于患者人群，我们将获得 大量的关于C.中白色 生物膜

DESCRIPTION (provided by the applicant): Candida-associated denture stomatitis (chronic atrophic candidiasis) is the most prevalent superficial oral infection and the most common form of Candida-associated disease. The etiology of denture stomatitis involves dental plaque. Dental plaque consists of a complex biofilm of bacteria and yeasts, predominantly Candida albicans. C. albicans biofilms have received much less attention than bacterial biofilms, and our present knowledge of their biology and drug resistance is at a rudimentary stage. Frequent denture stomatitis treatment failures combined with a steadily increasing population of elderly people, many of whom will be endentulous, make this area of study particularly important. The long-range goal of our work is to understand the biology and drug resistance of C. albicans biofilms. Our preliminary work in this new area resulted in the successful development of a reproducible model of C. albicans-associated biofilms (Publication #1). Since the last submission, we used this model to: 1) define the three stages of C. albicans associated biofilm development, 2) demonstrate that C. albicans biofilm is a highly heterogeneous structure, 3) show that the antifungal resistance of C. albicans biofilm increases in conjunction with biofilm development, 4) show that C. albicans has greater ability than the less pathogenic C. parapsilosis and Saccharomyces cerevisiae to form denture biofilm, and 5) show that C. albicans genes are differentially expressed under biofilm and planktonic conditions. Additionally, we initiated efforts to construct a C. albicans DNA array, and developed a bioprosthetic associated candidal biofilm model. Importantly, our studies showed that biofilm grown in our in vitro model has similar morphology as that growing in vivo on a catheter obtained from a patient with catheter-associated infection. Specific aims of the current proposal are: Specific Aim 1: Use our established biofilm model to determine the antifungal susceptibility profiles of C. albicans isolates obtained from denture stomatitis patients, and to study the effect of antifungal agents on the growth kinetics of C. albicans bioflims. Specific Aim 2: Investigate the mechanism(s) responsible for increased antifungal resistance of biofilm-associated C. albicans. Specific Aim 3: Identify genes that are involved in the formation and contribute to the development of antifungal resistance of C. albicans biofilms. By studying biofilm model systems and applying this knowledge to the patient population, we will gain a wealth of data about the biology and drug resistance of C. albicans in biofilms.