My laboratory is focused upon both basic science and clinically oriented projects involving members of the human oral flora. The two principal oral diseases, dental caries (tooth decay) and periodontitis, (gum disease) comprise the most common infectious diseases in all of humanity. Essentially every person will experience some form of one or both diseases during their lifetimes. Unlike most of the well-studied classical diseases of antiquity, oral diseases have polymicrobial etiologies and are derived from the host’s own flora, rather than foreign pathogens. Similar disease etiologies can be found in variety of other chronic infections of mucosal sites throughout the body. This has caused a major reassessment of how microbial pathogenesis is thought to occur in numerous human polymicrobial diseases because the standard therapeutic approaches, such as antibiotic treatment, vaccination, etc. have all met with limited success. The new paradigm for these infections is rooted in microbial ecology and differs significantly from the “one pathogen = one disease” dogma of the past 100 years. We are interested in the human oral system because it is the most accessible and tractable model system to investigate the principals underlying polymicrobial disease etiology.
The two model organisms we use for our basic science studies of the oral flora are Streptococcus mutans (associated with dental caries) and Fusobacterium nucleatum (associated with periodontitis). For S. mutans, we are currently focused upon two separate systems that were discovered by our group, which connect environmental sensory perception with adaptive gene regulation. Both sensory systems show great promise as useful therapeutic targets to reduce the prevalence of S. mutans in the oral cavity. Our studies of Fusobacterium nucleatum are focused upon the interactions of F. nucleatum with human cells and other bacterial species. F. nucleatum is highly unusual in its ability to tightly adhere to a vast array of bacteria and human cells through adhesins on its surface. We have found that this species has the ability to utilize molecular mimicry of human cells by adopting human glycosylation patterns on its outer surface. We are interested to determine how this process is regulated and what effect it has upon the host response to this organism.
For our clinically oriented research, we are focused upon two separate projects that are both aimed at determining whether human oral bacteria can seed distant infections throughout the body. Firstly, we are examining human diabetic foot infections to determine the species composition within active lesions, as there are some indications that members of the oral flora contribute to the disease. Diabetic ulcers are one of the most common side effects of diabetes and typically require surgical intervention to treat. Our second project involves the study of a previously uncultivated, unnamed species from the poorly studied genus Oribacterium. We are examining two human blood isolates that both triggered life-threatening septicemia. The Clinical Pathology Laboratory at the OUHSC was the first to isolate the organism and we have determined that the species potentially originates from the oral cavity. We are currently assembling the genome for the organism in hopes of creating better tools for molecular diagnostics for the species, as most hospital pathology laboratories would currently fail to detect this organism in afflicted patients.
Dr. Justin Merritt