Current tooth decay (dental caries) prevention methods include enamel hardening with fluoride and bacterial removal via mechanical and general antimicrobial approaches. These methods are based on the knowledge that oral plaque bacteria ferment dietary carbohydrates to produce pH-reducing organic acids. Initial reductions in caries incidence observed upon widespread implementation of these measures reached a plateaudecades ago. Today more that 40% of children under 10 years of age as well as more than 85% of the adult population in the United States still suffer from the disease that cause annual treatment cost of $ 80 billion. Further development of these "remove and kill all" approaches are not likely to significantly improve oral health. Revolutionary advancements can only be achieved by expanding our understanding of the microorganism- mediated processes leading to tooth decay. This will require a detailed picture of dental plaque organisms, their metabolic activities and interactions. The long-term objective of this application is to combine and apply (established) advanced technologies to provide a detailed understanding of the biological processes involved in cariogenesis. This will include a comprehensive analysis of the cariogenic potential of known pathogens and their influence on acid production. Furthermore, we will provide information on the metabolic activity of species whose function in acid production is currently unknown. In compliance with the mission of the NIDCR we will further develop targeted strategies against the current caries epidemic based on current knowledge and the new information developed with the advanced technologies in this project. We will combine sophisticated, species-specific in vivo labeling tools (monoclonal antibodies and fluorescent protein-expressing bacteria) with monitoring of acid production (pH-sensitive dyes, fluorescent proteins and NMR profiling), labeling of acid active species with stable isotope probing (SIP). These tools will reveal details of the processes in dental plaques regarding species, interspecies interactions and the metabolic processes contributing to cariogenic (acid-producing) or healthy (homeostatic) conditions. The second goal of this application will examine the potential of our previously developed specifically targeted antimicrobial peptides (STAMPs) against cariogenic Streptococcus mutans to shift plaque ecology towards a healthy plaque. We will further improve a current prototype antimicrobial peptide that is activated in acidic environments and develop more antimicrobial peptides against known cariogenic species as well as those identified in this project. This study will greatly expand our knowledge of the biological processes within plaques that lead to disease and provide novel therapeutic approaches that aim to achieve long-term oral health by specifically removing cariogenic species and leaving beneficial or harmless populations intact.

Public Health Relevance

Relevance to public health statement Tooth decay (caries) remains a major health issue in the United States and worldwide with a prevalence of more than 50% in young children that increases to about 85% in the adult population. The consequences of this disease range from a significant number missed days at school or work to malnutrition and effects on overall health, and result in about $80B in treatment costs. Caries disease-progression studies and resulting treatment regimen have not yielded significant oral-health improvements in several years. We propose to revisit the processes involved in caries development by combining carefully chosen and highly complementary new analytical and molecular biology tools. These tools will identify the roles of individual species and their characteristics involved in the acid production that leads to tooth decay. This new approach will provide a deeper understanding of tooth-decay progression and allow for the subsequent development of novel targeted therapeutic approaches to eliminate "bad" bacteria from the mouth for a long-term change to better oral health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE020102-03
Application #
8270368
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2010-05-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$382,004
Indirect Cost
$53,620
Name
University of California Los Angeles
Department
Dentistry
Type
Schools of Dentistry
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Guo, Lihong; Shi, Wenyuan (2013) Salivary biomarkers for caries risk assessment. J Calif Dent Assoc 41:107-9, 112-8
McLean, Jeffrey S; Lombardo, Mary-Jane; Ziegler, Michael G et al. (2013) Genome of the pathogen Porphyromonas gingivalis recovered from a biofilm in a hospital sink using a high-throughput single-cell genomics platform. Genome Res 23:867-77
Guo, Lihong; Hu, Wei; He, Xuesong et al. (2013) investigating acid production by Streptococcus mutans with a surface-displayed pH-sensitive green fluorescent protein. PLoS One 8:e57182
Guo, L; Wu, T; Hu, W et al. (2013) Phenotypic characterization of the foldase homologue PrsA in Streptococcus mutans. Mol Oral Microbiol 28:154-65
He, Xuesong; Hu, Wei; Kaplan, Christopher W et al. (2012) Adherence to streptococci facilitates Fusobacterium nucleatum integration into an oral microbial community. Microb Ecol 63:532-42
McLean, Jeffrey S; Fansler, Sarah J; Majors, Paul D et al. (2012) Identifying low pH active and lactate-utilizing taxa within oral microbiome communities from healthy children using stable isotope probing techniques. PLoS One 7:e32219
Hung, David C I; Downey, Jennifer S; Kreth, Jens et al. (2012) Oligomerization of the response regulator ComE from Streptococcus mutans is affected by phosphorylation. J Bacteriol 194:1127-35
Wang, Renke; Kaplan, Aida; Guo, Lihong et al. (2012) The influence of iron availability on human salivary microbial community composition. Microb Ecol 64:152-61

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