Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
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
2013-07-19
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712

  Publications

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
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
Ibberson, Carolyn B; Stacy, Apollo; Fleming, Derek et al. (2017) Co-infecting microorganisms dramatically alter pathogen gene essentiality during polymicrobial infection. Nat Microbiol 2:17079
Kuboniwa, Masae; Houser, John R; Hendrickson, Erik L et al. (2017) Metabolic crosstalk regulates Porphyromonas gingivalis colonization and virulence during oral polymicrobial infection. Nat Microbiol 2:1493-1499
Miller, Daniel P; Hutcherson, Justin A; Wang, Yan et al. (2017) Genes Contributing to Porphyromonas gingivalis Fitness in Abscess and Epithelial Cell Colonization Environments. Front Cell Infect Microbiol 7:378

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