Biology and Drug Resistance of Candida Biofilms

描述(申请人提供)：假丝酵母菌相关性义齿口炎 (慢性萎缩性念珠菌病)是最常见的浅表口腔感染 也是最常见的念珠菌相关疾病。义齿的病因学 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。白色念珠菌生物被膜 与细菌生物膜相比受到的关注要少得多，而我们现在 对它们的生物学和耐药性的了解还处于初级阶段。 频繁的义齿口炎治疗失败合并稳定的 不断增长的老年人人口，其中许多人将不辞劳苦，使 这一领域的研究尤为重要。我们工作的长远目标是 目的了解白色念珠菌生物被膜的生物学特性及耐药性。我们的 这一新领域的初步工作导致成功地开发了一种 白念珠菌相关生物膜的可复制模型(第1号出版物)。自.以来 在上一次提交时，我们使用这个模型来：1)定义了C。 与白念珠菌相关的生物膜发育，2)证明白念珠菌 生物膜是一种高度异质性的结构，3)表明抗真菌 白念珠菌生物被膜与生物被膜联合耐药 发展，4)表明白色念珠菌具有更强的能力 致病性近平葡萄球菌与酿酒酵母形成义齿 生物膜，以及5)表明白色念珠菌基因在 生物膜和浮游条件。此外，我们还开始努力 构建白念珠菌DNA阵列，研制出与白念珠菌相关的生物假体 念珠菌生物被膜模型。重要的是，我们的研究表明，生物膜生长在 我们的体外模型与体内导管上生长的模型具有相似的形态。 取自一名导管相关性感染患者。的具体目标 目前的建议是：具体目标1：利用我们建立的生物膜模型 白念珠菌分离株抗真菌药敏试验结果分析 取自义齿口腔炎患者，并研究其疗效。 抗真菌药物对白色念珠菌生物膜生长动力学的影响。特定目标 2：探讨抗真菌作用增强的机制(S) 生物膜相关白色念珠菌的耐药性。具体目标3：识别基因 参与形成并有助于发展的 白色念珠菌生物被膜的抗真菌耐药性。通过对生物膜模型的研究 系统，并将这些知识应用到患者群体中，我们将获得 年有关白色念珠菌生物学和耐药性的丰富数据 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.