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

$213,000R56FY2011DENIH

Lsu Health Sciences Center, New Orleans LA

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Abstract

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 is a fungal infection affecting approximately 50-75% of otherwise healthy denture wearers, and C. albicans is the most common cause of denture stomatitis. The role of Candida biofilms in denture stomatitis has been grossly understudied. The ability to study the pathogenic 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 this proposal is to optimize a new contemporary rat model of Candida-associated denture stomatitis, and characterize the role of the biofilm during infection and host response parameters that influence the development of disease. 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 Th1-type responses. The first specific aim of this project is to o optimize a new rat model of C. albicans denture stomatitis by accelerating disease onset. The second specific aim is to test the hypothesis that C. albicans biofilm formation on the denture plate and oral mucosa is required for development of denture stomatitis. The third specific aim is to test the hypothesis that the local Th1-type host response is induced and plays a role in the disease status.

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