Periodontal disease represents a group of inflammatory diseases, which lead to the destruction of the gingiva and the supporting structures of the teeth. The loss of tissue results from an imbalance of the host immune response induced by the colonization of specific sub-gingival bacteria. Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with periodontal disease and a variety of disseminated extra-oral infections. The multiple physiological niches occupied by this pathogen, sharing both common and unique properties, suggest that the expression of surface adhesins and other colonization genes are under strict transcriptional control. One of these genes, the extracellular matrix protein adhesin A (EmaA), is an important surface adhesin in biofilm biogenesis and disease initiation. We have acquired a strain that is responsive to the environmental regulation of emaA, and this strain will serve as a model system to determine the mechanism(s) used by this organism to maintain bacterial fitness in relation to the physiological niche. This infective endocarditis strain will be used in Aim One to identify transcriptional regulators of emaA and other genes associated with niche adaptation. We have also identified a novel process for EmaA regulation, and in Aim Two we will investigate this mechanism of intracellular regulation of emaA expression by the processed portion of the fimbrial subunit (Flp1). The new insights gained from understanding how A. actinomycetemcomitans regulates surface protein expression on a basal level as well as during physiological niche adaptation will aid in the development of molecules to disrupt and/or diminish tissue colonization by this pathogen.

Public Health Relevance

More than 80% of the population has some form of periodontal disease. The established relationship between oral and systemic disease makes combating periodontal disease a high priority for improving overall public health. In order to understand the relationship between oral and systemic disease, we need to define the specific mechanism by which bacteria regulate the transcription of genes encoding proteins important for infection. Our laboratory has identified a bacterial protein adhesin that is integral to the disease process. Insights into this adhesin and other proteins important for binding to host tissues and initiating infection will aid in the development of novel therapeutics to prevent initiation or progression of diseases, especially considering the increasing evolution of antibiotic resistant strains of bacteria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE029609-01
Application #
9958172
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Chander, Preethi
Project Start
2020-03-01
Project End
2022-02-28
Budget Start
2020-03-01
Budget End
2021-02-28
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405