Most bacterial pathogenesis studies have focused on mono-culture infections;however, it is clear that many bacterial infections are not simply the result of colonization with a single species, but rather ensue from the action of polymicrobial communities. Microbes within polymicrobial infections often display synergistic interactions that result in enhanced colonization and persistence in the infection site. Such interactions have been particularly noted in infections of the oral cavity, although the molecular processes controlling these synergistic interactions are generally not known. Detailed mechanistic studies elucidating the polymicrobial interactions necessary for enhanced persistence in vivo is critical for a comprehensive understanding of synergy, and a necessary first step towards developing therapeutics to treat polymicrobial infections. The overall goal of this research plan is to examine, from a mechanistic standpoint, how interactions between oral bacteria impact community development and in vivo persistence. To accomplish this goal, high-throughput genomics techniques will be employed to identify microbial virulence genes that are uniquely expressed during co-infection and/or required for polymicrobial synergy.

Public Health Relevance

The survival of pathogens in the human body has been rigorously studied for well over a century. Most bacterial pathogenesis studies have focused on mono-culture infections;however, it is clear that many bacterial infections are not simply the result of colonization with a single species, but are instead a result of colonization with several Microbes within polymicrobial infections often display synergistic interactions that result in enhanced colonization and persistence in the infection site. The goal of this research proposal is to utilize high throughput genomics techniques to elucidate the molecular basis of polymicrobial synergy in two model oral polymicrobial communities, with the ultimate goal of devising new therapeutic strategies for treating such infections.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DE023193-02
Application #
8704433
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
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Jorth, Peter; Turner, Keith H; Gumus, Pinar et al. (2014) Metatranscriptomics of the human oral microbiome during health and disease. MBio 5:e01012-14
Wright, Christopher J; Xue, Peng; Hirano, Takanori et al. (2014) Characterization of a bacterial tyrosine kinase in Porphyromonas gingivalis involved in polymicrobial synergy. Microbiologyopen 3:383-94
Murray, Justine L; Connell, Jodi L; Stacy, Apollo et al. (2014) Mechanisms of synergy in polymicrobial infections. J Microbiol 52:188-99
Wright, C J; Wu, H; Melander, R J et al. (2014) Disruption of heterotypic community development by Porphyromonas gingivalis with small molecule inhibitors. Mol Oral Microbiol 29:185-93