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.
Information gathered in these studies can be applied to other Candida mucosal and device-related biofilm infections, which can cause systemic infection and significant morbidity and mortality. Because biofilms are not only resistant to antimicrobial drugs but also to immune defenses, this knowledge base can be used to develop novel immunotherapies that target biofilm growth.
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