For many bacteria, humans are their only habitat, and evolution in these bacteria is in response to selective pressure from the host environment. As each human host represents a unique ecological niche, bacterial virulence factors that contribute to colonization and pathogenicity may need to be tailored to the specific host, in order to maximize fitness of the microorganism. Although all bacteria are able to diversify their genomes by random mutagenesis, species that also transfer DNA between strains have an added advantage in their ability to re-assort useful mutations into the same bacterial cell. Porphyromonas gingivalis is a Gram-negative anaerobe that colonizes plaque biofilms in the human subgingival crevice, and is a causative agent in the development of chronic and severe periodontal disease. P. gingivalis is a genetically diverse species, but little is known about how this diversity is generated, or how it contributes to the fitness of these important pathogens during chronic infections. The long-term goal of this project is to understand how genetic diversity contributes to fitness in chronic periodontal infections. As a first step towards this goal, the objective of this application is to determine the molecular mechanisms underlying genetic variability in P. gingivalis, and to measure the effect of DNA changes on bacterial fitness, using multi-species biofilm formation as a model system. These goals have been formulated based on a fundamental new behavior discovered in P. gingivalis: chromosomal DNA transfer between strains, which we hypothesize, is a major diversity generating mechanism for these oral pathogens. We will pursue the following three specific aims to address this hypothesis.
Aim One : Identify the genes that control horizontal transfer of chromosomal DNA in P. gingivalis.
Aim Two : Determine the prevalence of chromosomal DNA transfer within the species.
Aim Three : Identify genotypic changes that contribute to fitness improvements during P. gingivalis biofilm formation. The experiments described in this proposal will determine the effect of horizontal DNA transfer on complex bacterial phenotypes. The identification of bacterial genes that are transferred and favorably selected in response to environmental pressure will provide a novel framework for the identification of therapeutic targets for treatment of periodontal disease.

Public Health Relevance

Periodontal disease results from a long-term bacterial infection of the teeth and gums. Certain bacterial pathogens, such as Porphyromonas gingivalis, are able to avoid host immune responses, and are difficult to remove with manual cleaning methods as well as antibiotic treatments. Our research goals are to understand how genetic adaptation allows Porphyromonas gingivalis to persist in the human mouth. If we can understand what methods the bacteria are using to improve their fitness, then we can design better therapies for treating patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE019634-03
Application #
8230812
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2010-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$332,820
Indirect Cost
$110,070
Name
University of Texas Health Science Center Houston
Department
Dentistry
Type
Schools of Dentistry
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Kerr, Jennifer E; Abramian, Jared R; Dao, Doan-Hieu V et al. (2014) Genetic exchange of fimbrial alleles exemplifies the adaptive virulence strategy of Porphyromonas gingivalis. PLoS One 9:e91696
Tribble, Gena D; Kerr, Jennifer E; Wang, Bing-Yan (2013) Genetic diversity in the oral pathogen Porphyromonas gingivalis: molecular mechanisms and biological consequences. Future Microbiol 8:607-20
Olsen, Ingar; Tribble, Gena D; Fiehn, Nils-Erik et al. (2013) Bacterial sex in dental plaque. J Oral Microbiol 5:
Tribble, Gena D; Rigney, Todd W; Dao, Doan-Hieu V et al. (2012) Natural competence is a major mechanism for horizontal DNA transfer in the oral pathogen Porphyromonas gingivalis. MBio 3: