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)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
7R01DE023193-06
Application #
9594015
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2017-11-03
Project End
2019-05-31
Budget Start
2017-11-03
Budget End
2019-05-31
Support Year
6
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Georgia Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30318
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
Sztukowska, Maryta N; Dutton, Lindsay C; Delaney, Christopher et al. (2018) Community Development between Porphyromonas gingivalis and Candida albicans Mediated by InlJ and Als3. MBio 9:
Lamont, Richard J; Koo, Hyun; Hajishengallis, George (2018) The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol 16:745-759
Miller, D P; Wang, Q; Weinberg, A et al. (2018) Transcriptome analysis of Porphyromonas gingivalis and Acinetobacter baumannii in polymicrobial communities. Mol Oral Microbiol 33:364-377
Garg, Neha; Whiteley, Marvin (2018) The chemical topology of a bacterial swarm. J Biol Chem 293:9553-9554
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
Hendrickson, Erik L; Beck, David A C; Miller, Daniel P et al. (2017) Insights into Dynamic Polymicrobial Synergy Revealed by Time-Coursed RNA-Seq. Front Microbiol 8:261
Narayanan, Ajay M; Ramsey, Matthew M; Stacy, Apollo et al. (2017) Defining Genetic Fitness Determinants and Creating Genomic Resources for an Oral Pathogen. Appl Environ Microbiol 83:
Whiteley, Marvin; Diggle, Stephen P; Greenberg, E Peter (2017) Progress in and promise of bacterial quorum sensing research. Nature 551:313-320

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