The human oral cavity hosts at least 600 microbial species, many of which are uncultivated and whose roles in human health or disease remain unclear. This is especially true in the subgingival crevice where microbial communities interact through complex food webs forming structured metabolic guilds. These communities potentially lead to diseases of the mouth such as periodontitis, which affects approximately one third of the adult population. Recent, open-ended studies utilizing DNA-based methods have shed new light on the complex nature of subgingival microbial community structure. However, without advances in understanding the physiology of potentially key, uncultivated groups, treatment and more importantly, prevention of diseases such as periodontitis will remain difficult. To address this, we propose a hypothesis driven, targeted approach to selectively bring heretofore uncultivated, disease-associated microorganisms (e. g. candidate phyla TM7 and SR1) into study through advanced cell isolation and high-throughput cultivation techniques. We will employ a proven, immunological-based method, which has successfully been shown to capture rare and uncultivated microorganism from natural environments. This method leverages genomic information to synthesize surface antigens expressed by selected organisms thus avoiding a random approach to enrichment/cultivation. Novel isolates will be studied individually but more importantly, in combination with other species potentially serving as metabolite facilitators or syntrophs found in the same niche and health/disease state. Highly controllable microenvironments will be established using microfluidic systems that allow biofilm cultivation in conjunction with real-time, advanced imaging techniques. Model living hosts will also be established in Drosophila to simulate complex interactions in a biological system. These platforms will enable microcultivation of novel oral microbiota needed to establish integrated comparative and functional genomic studies, and will advance our understanding of the intimate interactions between microbes inhabiting the subgingival environment and their role in disease.
Periodontitis is a disease that affects the bone and tissues that support the teeth, leading to tooth loss and systemic diseases. It is caused by bacteria, but there are so many species in the mouth, many of them uncultured, that it has been difficult to figure out which ones cause disease and how different microbes interact and lead to heath or disease. The proposed studies will use microbial genomic information and advanced microbiological techniques to culture novel microbes and communities and to learn which bacteria are important so that ways to prevent and treat disease may be developed.
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