Document text
Principal Investigator: Randy B. Stockbridge
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2024
Award: $195,000
Funding agency: National Institute of Dental and Craniofacial Research
PROJECT SUMMARY/ABSTRACT
The problem: Dental caries is the leading health condition worldwide, affecting billions of people and causing
pain, impaired nutrition and social functioning, reduction in work/school productivity, and significant economic
impacts. For the most vulnerable groups, such as children and older adults, and individuals with high caries
risk of all ages, the consequences of this disease – including a reduced quality of life, morbidity and even
mortality – are unacceptable. Because caries is caused by the metabolism of dietary sugars by a cariogenic
biofilm, it is very difficult to control; the widespread consumption of fermentable sugars in modern diets favors
cariogenic species such as Streptococcus mutans and the opportunistic fungi Candida albicans in the dental
biofilm, perpetuating the caries process. Fluoride is the most effective agent for caries control, but it has very
limited antimicrobial effects because most microbes have membrane proteins to expel fluoride and keep
intracellular concentrations at sub-inhibitory levels. Different oral microbial species possess different types of
fluoride exporters; S. mutans and C. albicans employ CLCF and FEX proteins, respectively, while beneficial
oral streptococci use Fluc proteins. This creates an opportunity to specifically target pathogenic oral microbes
to modify species dynamics towards health-associated symbiotic communities in biofilms exposed to sugar and
fluoride. Hypothesis: We hypothesize that fluoride export proteins can be targeted for antimicrobial
development against cariogenic oral bacteria and fungi, while leaving beneficial oral microbiota intact. This
hypothesis will be tested in the following specific aims: S.A.#1: To evaluate the competitive fitness of fluoride
export-deficient strains of S. mutans and C. albicans in mixed-species biofilms under conditions of changing
fluoride and pH; S.A.#2: To identify natural products that potentiate fluoride toxicity for pathogenic oral
microbiota. Significance: The results of these studies will establish groundwork for the development of novel
caries treatments that potentiate the antimicrobial effects of fluoride ion, as well as provide new basic
knowledge about the role of fluoride and microbial fluoride resistance mechanisms in community dynamics of
the oral microbiota.
Terms: <0-11 years old><21+ years old><Adult><Adult Human><Affect><Age><Allergy><Antimicrobial Effect><Assay><Bacteria><Bioassay><Biochemical><Biodiversity><Biological Assay><Biological Diversity><Bionomics><Biosensor><Buccal Cavity><Buccal Cavity Head and Neck><C albicans><C. albicans><C.albicans><Candida albicans><Caries><Cavitas Oris><Chemicals><Chemosensitization><Chemosensitization/Potentiation><Child><Child Youth><Children (0-21)><Chlorhexidine><Communities><Complex Extracts><Consumption><Crude Extracts><Culture Media><Cytoplasm><Data><Dental Decay><Dental caries><Development><Diet><Dietary Sugars><Disease><Disorder><Ecology><Electrophysiology><Electrophysiology (science)><Exposure to><F- element><Family><Fluoride Ion><Fluorides><Gene Cluster><Generalized Growth><Genetic><Goals><Growth><Health><High Throughput Assay><Hypersensitivity><Impairment><Individual><Informatics><Intermediary Metabolism><Knock-out><Knockout><Knowledge><Lesion><Libraries><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Metabolic><Metabolic Processes><Metabolism><Microbe><Microbial Biofilms><Minerals><Modernization><Monitor><Morbidity><Morbidity - disease rate><Mouth><Natural Products><Neurophysiology / Electrophysiology><Non-Polyadenylated RNA><Oral><Oral cavity><Oral health><Output><Pain><Painful><Pathogenicity><Patients><Periodicals><Persons><Physiologic><Physiological><Potentiation><Process><Productivity><Protein Export><Protein Export Pathway><Proteins><QOL><Quality of life><RNA><RNA Gene Products><Ribonucleic Acid><Risk><Role><S gordonii><S mutans><S. gordonii><S. mutans><Schools><Social Functioning><Sorting><Specificity><Streptococcus gordonii><Streptococcus mutans><Surface Proteins><Testing><Tissue Growth><Toothpaste><Toxic effect><Toxicities><Variant><Variation><Vulnerable Populations><Work><Yeasts><adulthood><ages><anti-microbial><anti-microbial effect><anticaries><antimicrobial><biofilm><biofilm community><biofilm species><biological sensor><cariogenic biofilm><complex extract><dental agent><dental biofilm><dental health><developmental><diets><dysbacteriosis><dysbiosis><dysbiotic><economic impact><electrophysiological><experiment><experimental research><experimental study><experiments><fitness><function socially><functioning social><fungus><genetic profiling><growth media><high throughput screening><improved><kids><microbial><microbial composition><microbial imbalance><mixed species biofilm><mortality><multi-microorganism biofilm><multispecies biofilm><naturally occurring product><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><nutrition><older adult><older adulthood><ontogeny><oral bacteria><oral biofilm><oral flora><oral microbial community><oral microbiota><oral microflora><oral pathogen><oral streptococci><periodic><periodical><physiologic model><plaque biofilm><polymicrobial biofilm><prevent><preventing><resistance mechanism><resistant mechanism><side effect><social role><sugar><tooth decay><vulnerable group><vulnerable individual><vulnerable people><youngster>