Periodontal disease is caused by bacterial pathogens that thrive in a complex multi-species community that forms in the gingival pocket. The initiation and growth of this biofilm requires sophisticated molecular communication among the species in this community. We have shown that the periodontal pathogens A. actinomycetemcomitans and P.gingivalis produce the quorum sensing signal autoinducer2 (AI-2) which may be involved in intra- and interspecies communication among these organisms. AI-2 regulates genes involved in virulence, iron acquisition and biofilm formation and is likely an important mechanism that allows these organisms to sense and respond to their local environment. Our general hypothesis that A. actinomycetemcomitans and P. gingivalis respond differentially to AI-2 and the outcomes of these signaling systems are tailored to the specific survival strategies that are employed by these organisms in the oral biofilm. The long term goal of this proposal is to determine if AI-2 quorum sensing can be exploited to control oral biofilm development.
The specific aims are to characterize the AI-2 receptors and early events that initiate the cellular response to AI-2 of A. actinomycetemcomitans and P. gingivalis since these are ideal targets for therapeutic intervention. We will determine if importation and intracellular processing of AI-2 is required to initiate the cellular response. The QseBC and GppX two component signaling systems of A. actinomycetemcomitans and P. gingivalis respectively, will be studied to determine if they couple the detection of AI-2 to downstream gene regulatory events. Finally, we will determine if the function of high and low affinity AI-2 receptors in A. actinomycetemcomitans facilitate colonization of both early and mature biofilms by this organism. These studies will define at the molecular level how oral pathogens detect and interact with AI-2 and how these processes lead to alteration in gene expression that facilitates their growth in microbial communities. This information may facilitate the rational design of new therapeutics that may control the growth and development of oral microbial biofilms by interfering with their communication pathways.

Public Health Relevance

Periodontitis is a common oral disease that is present in up to 40% of the adult population in the United States and annual expenditures for treatment and prevention of periodontitis are over $14 billion. Periodontitis caused by a community of bacteria that live in the gingival pocket, but it is also associated with systemic illnesses such as heart disease. Preventing periodontal disease requires eliminating or controlling the microbial community. Our studies examine a unique microbial communication pathway that facilitates the development of the bacterial community. We seek to develop new potential drugs that prevent the formation of microbial communities by interfering with this communication system in order to control or prevent periodontitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE014605-11
Application #
8299184
Study Section
Special Emphasis Panel (ZRG1-MOSS-E (02))
Program Officer
Lunsford, Dwayne
Project Start
2002-04-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
11
Fiscal Year
2012
Total Cost
$349,758
Indirect Cost
$71,283
Name
University of Louisville
Department
Dentistry
Type
Schools of Dentistry
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Torres-Escobar, Ascención; Juárez-Rodríguez, María D; Demuth, Donald R (2014) Integration host factor is required for replication of pYGK-derived plasmids in Aggregatibacter actinomycetemcomitans. FEMS Microbiol Lett 357:184-94
Torres-Escobar, Ascención; Juárez-Rodríguez, María Dolores; Demuth, Donald R (2014) Differential transcriptional regulation of Aggregatibacter actinomycetemcomitans lsrACDBFG and lsrRK operons by integration host factor protein. J Bacteriol 196:1597-607
Juarez-Rodriguez, Maria Dolores; Torres-Escobar, Ascencion; Demuth, Donald R (2013) ygiW and qseBC are co-expressed in Aggregatibacter actinomycetemcomitans and regulate biofilm growth. Microbiology 159:989-1001
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Juarez-Rodriguez, Maria Dolores; Torres-Escobar, Ascencion; Demuth, Donald R (2013) Construction of new cloning, lacZ reporter and scarless-markerless suicide vectors for genetic studies in Aggregatibacter actinomycetemcomitans. Plasmid 69:211-22
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Chawla, Aarti; Hirano, Takanori; Bainbridge, Brian W et al. (2010) Community signalling between Streptococcus gordonii and Porphyromonas gingivalis is controlled by the transcriptional regulator CdhR. Mol Microbiol 78:1510-22
Shao, HanJuan; Demuth, Donald R (2010) Quorum sensing regulation of biofilm growth and gene expression by oral bacteria and periodontal pathogens. Periodontol 2000 52:53-67

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