Identification of cyclic di-GMP signaling components in P. gingivalis Cyclic dimeric GMP (c-di-GMP) has been considered as one of the most common bacterial second messengers. A growing body of evidence shows that c-di-GMP regulates bacterial cell cycle, differentiation, biofilm formation and dispersion, and virulence. One of important features of c-di-GMP is that it is a unique second messenger only found in bacteria and lower eukaryotes. From a practical standpoint, modulation of c- di-GMP signal pathways may provide a new target of controlling bacterial infection. Although there is a huge interest in c-di-GMP sweeping through microbiology, especially in the role of c-di-GMP signaling in bacterial biofilm formation and dispersion, the study of c-di-GMP signaling in oral bacteria is very limited. Recently, we have initiated investigation of c-di-GMP signaling in Porphyromonas gingivalis, likely due to none of genes is annotated encoding a diguanylate cyclase. Using bioinformatics tools, we found a protein containing a GGDEF domain with high certainty, PGN_1932 (previously annotated as a conserved hypothetical protein). Our objective of this application is to determine the role of cyclic di-GMP in regulation of cellular functions of P. gingivalis. We hypothesize that c-di-GMP signaling plays an important role in controlling biofilm formation and the virulence of P. gingivalis through regulation of c-di-GMP level, its metabolic enzymes and receptors. To test this hypothesis, we will first confirm the diguanylate cyclase activity of a putative DGC protein (PGN_1932) and examine correlation of the c-di-GMP concentration with phenotypic output, emphasizing on biofilm formation of P. gingivalis. We will seek to validate c-di-GMP targets. Our laboratory is committed to understanding c-di-GMP signaling in P. gingivalis because of its importance in the bacterial virulence, especially in bioflm formation and invasion of epithelial cells. The proposed studies on cyclic di-GMP will lead to a deeper understanding of how P. gingivalis use this signaling molecule to response to environmental stimulators and to communicate with host cells. Deciphering of the role of c-di-GMP in P. gingivalis pathogenicity may provide bases for developing new strategies of preventing and treating biofilm induced periodontitis.

Public Health Relevance

Periodontitis is one of the most widespread infectious diseases in adulthood, with an estimated 5 -20% of the world's population suffering from generalized chronic periodontitis. P. gingivalis infection is involved in the initiation and progression of periodontitis. The studies proposed here to understand the role of c-di-GMP in regulation of the bacterial virulence, especially in biofilm formation and invasion of epithelial cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE025332-01
Application #
8948572
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2015-07-01
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Meharry Medical College
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
041438185
City
Nashville
State
TN
Country
United States
Zip Code
37208