Adult periodontitis is disproportionally distributed among races, and has a significantly higher incidence in non- Hispanic blacks compared to non-Hispanic whites, even when co-variates such as diabetes and other health and social factors have been taken into account. Titers to the oral pathogen P. gingivalis are reported to be higher, as anticipated, in dentate subjects with, compared to those without periodontitis. Our laboratory was to first to report an intergeneric communication between Streptococcus cristatus and P. gingivalis. We identified a surface protein of S. cristatus, arginine deiminase (ArcA), as a signal molecule to which P. gingivalis responds by repressing the expression of the fimA gene, which codes for the major subunit protein of long fimbriae. The latter is required for bacterial colonization of P. gingivalis and host cell invasion. Therefore this project will test the hypothess that: a) S. cristatus serves as a beneficial bacterium and plays an important role in the prevention of P. gingivalis colonization of the oral cavity;and b) that the increased incidence of periodontitis in African-Americans may be due to either a decreased ratio of oral S. cristatus: P. gingivalis in these subjects compared to whites, or that the FimA genotypes may differ in blacks vs. whites.
Our aims therefore are to: 1) determine the distribution of S. cristatus and P. gingivalis in dental plaques of those with moderate periodontitis, severe periodontitis and periodontal healthy individuals, and compare microbial profiles (especially S. cristatus and P. gingivalis), in Africa Americans versus Caucasians within each group;and 2) to examine the correlation of these prevalence of S. cristatus and P. gingivalis with different FimA genotypes. To achieve these aims, we will recruit three groups of subjects: those with a healthy periodontium, or with moderate versus severe periodontitis. Each group will be composed of adult African American and Caucasian males and females. Exclusion criteria will include diabetes, HIV-AIDs and other health criteria such as pregnancy. All subjects will receive a full-mouth examination of periodontal status and a medical history. Microbial samples from dental plaque will be collected. The prevalence of S. cristatus and P. gingivalis will be determined by qPCR analysis, as will the prevalence of different FimA genotypes. We anticipate that the proposed studies will provide important information regarding the pathogenesis of periodontitis, and the microbial biofilms found in these two populations and will pave the way for extended studies in future, focused in the longer term on the development of appropriate interventional strategies targeting at eliminating of P. gingivalis colonization.

Public Health Relevance

Porphyromonas gingivalis is a primary pathogen associated with adult periodontitis affecting a large proportion of the population, and African Americans are more likely to exhibit periodontitis than whites with odds ratio between 2.09 and 2.4 in US adults. The goal of this proposal is to investigate microbial profiles of moderate periodontitis, severe periodontitis and periodontal health individuals in African Americans and Caucasians. Findings from this work will significantly enhance our understanding of the key role of indigenous microbial communities in influencing human health and health disparities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DE022428-02
Application #
8471686
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2012-05-21
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$176,160
Indirect Cost
$43,680
Name
Meharry Medical College
Department
Dentistry
Type
Schools of Dentistry
DUNS #
041438185
City
Nashville
State
TN
Country
United States
Zip Code
37208
Ho, Meng-Hsuan; Lamont, Richard J; Chazin, Walter J et al. (2018) Characterization and development of SAPP as a specific peptidic inhibitor that targets Porphyromonas gingivalis. Mol Oral Microbiol 33:430-439
Dong, Xin-Hong; Ho, Meng-Hsuan; Liu, Bindong et al. (2018) Role of Porphyromonas gingivalis outer membrane vesicles in oral mucosal transmission of HIV. Sci Rep 8:8812
Ho, Meng-Hsuan; Lamont, Richard J; Xie, Hua (2017) A novel peptidic inhibitor derived from Streptococcus cristatus ArcA attenuates virulence potential of Porphyromonas gingivalis. Sci Rep 7:16217
Ho, Meng-Hsuan; Lamont, Richard J; Xie, Hua (2017) Identification of Streptococcus cristatus peptides that repress expression of virulence genes in Porphyromonas gingivalis. Sci Rep 7:1413
Ho, Meng-Hsuan; Huang, Li; Goodwin, J Shawn et al. (2016) Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis. PLoS One 11:e0149618
Ho, Meng-Hsuan; Guo, Zhong-Mao; Chunga, Julio et al. (2016) Characterization of Innate Immune Responses of Human Endothelial Cells Induced by Porphyromonas gingivalis and Their Derived Outer Membrane Vesicles. Front Cell Infect Microbiol 6:139
Ho, Meng-Hsuan; Chen, Chin-Ho; Goodwin, J Shawn et al. (2015) Functional Advantages of Porphyromonas gingivalis Vesicles. PLoS One 10:e0123448
Mantri, Chinmay K; Chen, Chin-Ho; Dong, Xinhong et al. (2015) Fimbriae-mediated outer membrane vesicle production and invasion of Porphyromonas gingivalis. Microbiologyopen 4:53-65
Xie, H (2015) Biogenesis and function of Porphyromonas gingivalis outer membrane vesicles. Future Microbiol 10:1517-27
Chaudhuri, Swarnava; Pratap, Siddharth; Paromov, Victor et al. (2014) Identification of a diguanylate cyclase and its role in Porphyromonas gingivalis virulence. Infect Immun 82:2728-35

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