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

描述(申请人提供)：人们对生物膜在传染病中的作用产生了极大的兴趣。据估计，80%的人类感染是由病原生物膜引起的。白色念珠菌很容易在非生物表面形成生物膜，包括用于制造假牙的表面。此外，我们实验室的最新数据表明，白色念珠菌在体内的粘膜组织等生物表面形成了生物膜。义齿口炎(DS)是一种真菌感染，影响约50%-75%的其他健康义齿佩戴者，而白色念珠菌是义齿口炎最常见的原因。白色念珠菌很容易在义齿材料上形成生物膜；然而，生物膜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相关设备相关或粘膜疾病模型中的作用的能力受到了限制，因为很难找到合适的、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。这些研究的目的是确定单微生物和多微生物生物膜在念珠菌相关DS中的作用，并利用我们创新的DS大鼠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，假丝酵母菌生物膜的形成在义齿口腔炎中起重要作用，它通过从义齿持续接种口腔粘膜而导致组织相关生物膜的形成和由于不受控制的先天和适应性反应而导致的慢性红斑性炎症。这个项目的第一个具体目标是测试假牙上白色念珠菌生物膜的形成和 口腔粘膜是义齿口炎发生所必需的。第二个具体目标是检验局部先天和适应性宿主反应有助于疾病病理的假设。第三个具体目标是检验假体白念珠菌和光滑念珠菌混合感染可加速义齿口腔炎病情进展的假说。

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.