Overview

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. This four year project funded through the NIH National Institute of Dental and Craniofacial Research (NIDCR) propose to revisit the processes involved in caries development by combining carefully chosen and highly complementary new analytical and molecular biology tools.

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 plateau decades 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. 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.

In this project we seek to combine modern techniques in a systems biology approach using species-specific in vivo labeling tools (monoclonal antibodies and fluorescent protein-expressing bacteria), monitoring of acid production (pH-sensitive dyes, fluorescent proteins and metabolite profiling), as well as ecology based approaches such as labeling of acid active species with stable isotope probing (SIP) combined with deep 16S rRNA pyrosequencing. These combined approaches 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 previously developed specifically targeted antimicrobial peptides (STAMPs) against cariogenic Streptococcus mutans by the UCLA team to shift plaque ecology towards a healthy plaque. We will further improve a current prototype antimicrobial peptides 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.

Funding

National Institutes of Health (NIH) National Institute of Dental and Craniofacial Research (NIDCR)

Jeffrey McLean

Renate Lux and
Wenyuan Shi
University of California Los Angeles

Confocal Laser Scanning micrograph of mixed species in oral plaque bacterial community which can contain >600 species.

Image: Jeffrey McLean / JCVI