Periodontal disease, one of the most common infections of humans, has a polymicrobial etiology whereby groups of microorganisms exhibit synergistic pathogenicity. As a model system for the study of polymicrobial synergy we are investigating P. gingivalis-S. gordonii interactions. S. gordonii, an early colonizer of the plaque biofilm, provides an attachment substratum for the more pathogenic later colonizer P. gingivalis. Contact dependent signaling and metabolite perception initiate further accumulation of P. gingivalis and the development of a dual species community. Interspecies coadhesion is mediated by the short fimbriae (comprised of the Mfa1 structural subunit) of P. gingivalis that engage the Ssp surface proteins of S. gordonii. Within SspB several amino acid motifs within a region spanning residues 1167-1193 (designated BAR), dictate binding activity and specificity. Development, and later constraint, of community development depends on the balance of tyrosine phosphorylation (through the kinase Ptk1) and dephosphorylation (through the phosphatase Ltp1) within P. gingivalis, which controls expression of community effectors such as Mfa1 and LuxS. This tyrosine (de)phosphorylation dependent signal transduction pathway also converges on the expression genes encoding proteases, and a dual species community of P. gingivalis and S. gordonii is more pathogenic compared to either species alone in a murine alveolar bone loss model. The objectives of this study are to: i) characterize the structural and functional motifs of Mfa1 that interact with the BAR domain of SspB;ii) define the role of the P. gingivalis tyrosine kinase Ptk1 in regulatory networks that control heterotypic community development with S. gordonii;and iii) determine the responses of P. gingivalis to the streptococcal metabolite 4-aminobenzoate (pABA) that regulate community development and pathogenic potential. Successful completion of these objectives will provide novel structure and function information on the P. gingivalis Mfa1 fimbrial adhesin. In addition, we will unravel the interplay between tyrosine kinase (Ptk1) and phosphatase (Ltp1) activities in the signal transduction events that regulate community development. We will also generate novel information regarding metabolite sensing and its role in both community development and pathogenic potential. Our broad long-term goal is to translate this fundamental mechanistic information into the identification of novel targets for therapeutic intervention directed toward pathogenic community inhibition. As single target intervention can have limited utility, and has yet to yield any significant advances in periodontal therapeutic options, interference with multiple components of pathogenic community development, including adhesive and maturation events, may have a greater likelihood of success.

Public Health Relevance

Information that will be obtained from this study has the potential to be translated into the development of toothpastes or mouthrinses that can prevent disease causing organisms from accumulating on the teeth. These would reduce the ability of disease causing bacteria to persist in the mouth and consequently prevent or reduce the severity of gum disease.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lunsford, Dwayne
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Louisville
Schools of Dentistry/Oral Hygn
United States
Zip Code
Liu, C; Miller, D P; Wang, Y et al. (2016) Structure-function aspects of the Porphyromonas gingivalis tyrosine kinase Ptk1. Mol Oral Microbiol :
Rego, Sara; Heal, Timothy J; Pidwill, Grace R et al. (2016) Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae. J Biol Chem 291:15985-6000
Sztukowska, Maryta N; Ojo, Akintunde; Ahmed, Saira et al. (2016) Porphyromonas gingivalis initiates a mesenchymal-like transition through ZEB1 in gingival epithelial cells. Cell Microbiol 18:844-58
Hajishengallis, George; Lamont, Richard J (2016) Dancing with the Stars: How Choreographed Bacterial Interactions Dictate Nososymbiocity and Give Rise to Keystone Pathogens, Accessory Pathogens, and Pathobionts. Trends Microbiol 24:477-89
Hasegawa, Y; Iijima, Y; Persson, K et al. (2016) Role of Mfa5 in Expression of Mfa1 Fimbriae in Porphyromonas gingivalis. J Dent Res 95:1291-7
Hutcherson, J A; Gogeneni, H; Yoder-Himes, D et al. (2016) Comparison of inherently essential genes of Porphyromonas gingivalis identified in two transposon-sequencing libraries. Mol Oral Microbiol 31:354-64
Lamont, Richard J; Hajishengallis, George (2015) Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med 21:172-83
Richards, A M; Abu Kwaik, Y; Lamont, R J (2015) Code blue: Acinetobacter baumannii, a nosocomial pathogen with a role in the oral cavity. Mol Oral Microbiol 30:2-15
Scheres, Nina; Lamont, Richard J; Crielaard, Wim et al. (2015) LuxS signaling in Porphyromonas gingivalis-host interactions. Anaerobe 35:3-9
Ikai, Ryota; Hasegawa, Yoshiaki; Izumigawa, Masashi et al. (2015) Mfa4, an Accessory Protein of Mfa1 Fimbriae, Modulates Fimbrial Biogenesis, Cell Auto-Aggregation, and Biofilm Formation in Porphyromonas gingivalis. PLoS One 10:e0139454

Showing the most recent 10 out of 61 publications