In many instances the encounter between host and microbial cells can be, through a longstanding evolutionary association, a balanced interaction whereby both cell types co-exist and inflict a minimal degree of harm on each other. Disease will only ensue when this balance is disrupted from the microbe's perspective, and/or as a result of, for example, """"""""unintended"""""""" (in an evolutionary sense) consequences of immune or other host cell activity. This project proposes to study these intricate cellular interactions occurring between oral epithelial cells and important plaque microorganisms.
In Specific Aim 1, we will assemble a baseline transcriptional profile of gingival epithelial cells in co-culture with Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, two important periodontal pathogens. Human DNA microarrays will be used as a platform technology in addition to bioinformatics, statistical and ontology tools, to uncover highly significant genes and pathways of the host that are modulated upon microbial-host interaction. We will then, in the second Specific Aim, investigate at the molecular level the contribution of specific microbial genes to these complex interactions using a microbial mutant analysis approach. These studies will dissect selected host pathways related to bacterial adhesion, invasion and toxicity, and will confirm the transcriptional data at the protein and functional level. In the third Specific Aim, we will use mixed microbiota to compare the host's response to a complex microbial challenge. This will be done to assess if synergistic or antagonistic effects can be ascribed to combinations of challenging microorganisms, and investigate if there is a protective effect associated with the """"""""good"""""""" microflora, represented here by Streptococcus gordonii. Phenotypic assays will be complemented with transcriptional profiles to address the effect of an increasingly complex flora on the host's response to microbial challenges. These studies are anticipated to help dissect the complex and dynamic interaction between the oral microflora and its host, which may lead, in the long run, to the development of novel, rational and practical therapeutic, prophylactic and diagnostic applications. Relevance to public health: This work proposes to study the interactions that occur in the oral cavity between microbes and the mucosal surface. Using state-of-the-art technology, we intend to characterize the entire set of host genes and pathways that are modulated in response to relevant microbial challenges. This study is expected to provide new avenues for therapies and diagnostics for periodontal diseases. This is particularly timely considering the recent association between the oral health and certain cardio-vascular diseases. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016715-02
Application #
7188097
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2006-02-21
Project End
2011-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
2
Fiscal Year
2007
Total Cost
$271,995
Indirect Cost
Name
University of Florida
Department
Dentistry
Type
Schools of Dentistry
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Alaoui-El-Azher, Mounia; Mans, Jeffrey J; Baker, Henry V et al. (2010) Role of the ATM-checkpoint kinase 2 pathway in CDT-mediated apoptosis of gingival epithelial cells. PLoS One 5:e11714
Mans, Jeffrey J; Hendrickson, Erik L; Hackett, Murray et al. (2010) Cellular and bacterial profiles associated with oral epithelium-microbiota interactions. Periodontol 2000 52:207-17
Mans, Jeffrey J; von Lackum, Kate; Dorsey, Cassandra et al. (2009) The degree of microbiome complexity influences the epithelial response to infection. BMC Genomics 10:380
Papapanou, Panos N; Behle, Jan H; Kebschull, Moritz et al. (2009) Subgingival bacterial colonization profiles correlate with gingival tissue gene expression. BMC Microbiol 9:221
Demmer, Ryan T; Behle, Jan H; Wolf, Dana L et al. (2008) Transcriptomes in healthy and diseased gingival tissues. J Periodontol 79:2112-24
Hasegawa, Yoshiaki; Tribble, Gena D; Baker, Henry V et al. (2008) Role of Porphyromonas gingivalis SerB in gingival epithelial cell cytoskeletal remodeling and cytokine production. Infect Immun 76:2420-7
Handfield, M; Baker, H V; Lamont, R J (2008) Beyond good and evil in the oral cavity: insights into host-microbe relationships derived from transcriptional profiling of gingival cells. J Dent Res 87:203-23
Mao, Song; Park, Yoonsuk; Hasegawa, Yoshiaki et al. (2007) Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis. Cell Microbiol 9:1997-2007
Hasegawa, Yoshiaki; Mans, Jeffrey J; Mao, Song et al. (2007) Gingival epithelial cell transcriptional responses to commensal and opportunistic oral microbial species. Infect Immun 75:2540-7
Mans, Jeffrey J; Lamont, Richard J; Handfield, Martin (2006) Microarray analysis of human epithelial cell responses to bacterial interaction. Infect Disord Drug Targets 6:299-309