Defense Date


Document Type


Degree Name

Master of Science


Microbiology & Immunology

First Advisor

Daniel Miller

Second Advisor

Michael McVoy

Third Advisor

Richard Marconi


Periodontitis is a form of oral disease characterized by dysbiosis of the oral microbiome, leading to inflammation, bone resorption, and in severe cases, entire tooth loss, affecting 42% of adults in the US. One of the bacteria most associated with periodontal disease progression is Treponema denticola (Td), an oral spirochete which inhabits the mouth in small quantities during health but which can dominate the biofilms that form during periodontal disease. The ability of Td to survive in a disease environment and contribute to the progression of disease requires the use of robust signaling networks. Analysis of Td cultures revealed the existence of a potential regulatory signaling network in Td, one using the nucleotide-based second messenger molecule cyclic-di-AMP (c-di-AMP), and further allowed for characterizing a diadenylate cyclase enzyme responsible for its synthesis in Td, along with a potential regulator of diadenylate cyclase activity. This enzyme was shown to be encoded in the genomes of a variety of Td strains and other species of treponemes. This opens for study a wide range of signaling pathways and responses which may be based on c-di-AMP, which is capable of regulating growth, physiology, and virulence. These data help provide, for the first time, evidence for the existence of c-di-AMP in Td, and presents a new set of targets for treatment of Td infection.


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