Streptococcus sanguinis and Streptococcus gordonii are considered health beneficial early colonizers of the oral biofilm. Their initial attachment influences subsequent biofilm development and species composition. The clinical relevant antagonism between commensals S. sanguinis and S. gordonii with cariogenic Streptococcus mutans provides the unique possibility to develop alternative strategies in oral disease prevention. Increasing S. sanguinis and S. gordonii competitiveness over cariogenic species like S. mutans could manipulate oral biofilm development towards a healthy composition. We recently identified pyruvate oxidase (SpxB) dependent hydrogen peroxide production by S. sanguinis and S. gordonii as major competitive factor in interspecies interactions with S. mutans. Furthermore, hydrogen peroxide induces the release of extracellular DNA required for biofilm formation. To better understand the role of hydrogen peroxide in these processes, we propose to: 1) elucidate the differences in the regulatory mechanisms of H2O2 production and self-compatibility by H2O2 producers, 2) elucidate the functional relationship between SpxB dependent H2O2 production, eDNA release and biofilm formation and 3) and probe ecological significance of SpxB in vivo at the host-bacterial interface in a novel murine model. This research provides an innovative approach to study the role of pyruvate oxidase dependent hydrogen peroxide production employing genomic, global transcription, protein interaction, and biostatistics data. The results of this research will provide an enhanced understanding of how environmental factors and the biofilm mode of growth in a multispecies setting influence the major competitive factor of oral commensals. Importantly, these studies directly link molecular analysis to biological significance. The goal is to use the gained information to increase oral commensal competitiveness, e.g. increasing hydrogen peroxide production under competitive conditions. This understanding should provide important new insight into the development of new strategies to prevent oral diseases.

Public Health Relevance

Streptococcus sanguinis and Streptococcus gordonii are important members of the oral biofilm community. An increased abundance of those oral commensals relative to cariogenic species like Streptococcus mutans has been shown beneficial for the host in regard to disease development. Strong experimental evidence suggest that this inverse relationship is determined by the production of S. mutans-inhibiting amounts of hydrogen peroxide (H2O2) by S. sanguinis and S. gordonii, providing a competitive advantage during early biofilm formation. H2O2 is produced by the pyruvate oxidase (SpxB). H2O2 production also initiates the release of extracellular DNA (eDNA), which promotes cell-cell aggregation and biofilm formation. The central hypothesis of this proposal is that SpxB dependent H2O2 production and eDNA release are crucial early events that prevent an ecological shift favoring cariogenic species. In depth analysis of the regulation of spxB gene expression and H2O2 production combined with an in vivo investigation of biological relevance using a novel murine model will allow us to modulate biofilm formation towards a healthy composition. This will provide a new strategy to prevent oral diseases like caries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE021726-01A1
Application #
8631680
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2014-03-06
Project End
2019-02-28
Budget Start
2014-03-06
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$370,000
Indirect Cost
$120,000
Name
University of Oklahoma Health Sciences Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
Roberts, Adam P; Kreth, Jens (2014) The impact of horizontal gene transfer on the adaptive ability of the human oral microbiome. Front Cell Infect Microbiol 4:124