The role of Candida albicans biofilms in a novel rat model of denture stomatitis

描述（由申请人提供）：生物膜在传染病中的作用引起了极大的兴趣。据估计，80%的人类感染是由致病性生物膜引起的。白色念珠菌很容易在非生物表面形成生物膜，包括用于制作假牙的表面。此外，我们实验室最近的数据表明，白色念珠菌在生物表面形成生物膜，如体内粘膜组织。假牙口炎（DS）是一种真菌感染，影响了大约50-75%的健康假牙佩戴者，白色念珠菌是引起假牙口炎的最常见原因。白色念珠菌容易在义齿材料上形成生物膜；然而，生物膜的形成在义齿口炎发病机制中的作用尚不清楚。研究白色念珠菌生物膜在器械相关疾病或粘膜疾病的相关模型中的作用的能力受到限制，因为难以确定一种合适的、负担得起的、易于进入感染部位的动物模型。本研究的长期目标是了解宿主和念珠菌之间的相互作用如何促进粘膜疾病的发展，并确定针对生物膜的治疗策略，以减少疾病状态的发生率。这些研究的目的是确定单微生物和多微生物生物膜形成在念珠菌相关的DS中的作用，并利用我们的创新大鼠DS模型表征影响疾病发展的宿主反应参数。我们的中心假设是念珠菌生物膜的形成在义齿口炎中起着重要的作用，通过义齿持续接种口腔黏膜，导致组织相关的生物膜形成和慢性红斑性炎症，这是由于先天和适应性反应不受控制。这个项目的第一个具体目的是测试白色念珠菌生物膜在义齿上形成的假设

DESCRIPTION (provided by applicant): There has been a tremendous interest in the role of biofilms on infectious diseases. It is estimated that 80% of human infections result from pathogenic biofilms. Candida albicans readily forms biofilms on abiotic surfaces, including those used to make dentures. In addition, recent data from our laboratory indicates that C. albicans forms biofilms on biotic surfaces such as mucosal tissue in vivo. Denture stomatitis (DS) is a fungal infection affecting approximately 50-75% of otherwise healthy denture wearers, and C. albicans is the most common cause of denture stomatitis. C. albicans readily forms biofilm on denture materials; however, the role of biofilm formation in the pathogenesis of denture stomatitis is unknown. The ability to investigate the role of C. albicans biofilms in a relevant model of device-associated or mucosal disease has been limited by difficulty in identifying an appropriate, affordable animal model with ease of access to the site of infection. The long-term goal of this research is to understand how the interaction between the host and Candida contribute to development of mucosal disease and to identify therapeutic strategies targeted toward the biofilm to reduce the incidence of the disease state. The objective of these studies is to determine the role of monomicrobial and polymicrobial biofilm formation in Candida-associated DS and characterize host response parameters that influence the development of disease using our innovative rat model of DS. Our central hypothesis is that Candida biofilm formation plays a significant role in denture stomatitis through the continuous inoculation of the oral mucosa from the denture leading to tissue-associated biofilm formation and chronic erythematous inflammation due to uncontrolled innate and adaptive responses. The first specific aim of this project is to test the hypothesis that C. albicans biofilm formation on the denture and oral mucosa is required for development of denture stomatitis. The second specific aim is to test the hypothesis that the local innate and adaptive host response contributes to disease pathology. The third specific aim is to test the hypothesis that mixed species infection with C. albicans and C. glabrata accelerates disease progression in denture stomatitis.