All ETDs from UAB

Advisory Committee Chair

Hui Wu

Advisory Committee Members

William H Benjamin

Christian Melander

Suzanne Michalek

Moon Nahm

Document Type

Dissertation

Date of Award

2016

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Dental caries, commonly known as tooth decay, is characterized by the destruction of the tooth’s hydroxyapatite, the primary mineral of enamel. Tooth decay is caused by the combination of poor salivary flow, frequent dietary sugar intake, poor dental hygiene, and the prevalence of cariogenic bacteria. Exposure to sucrose promotes Streptococcus mutans to form a cariogenic biofilm, which is the major risk factor for dental caries. Currently there are no anticaries therapies that selectively target S. mutans biofilms. In this study, we identified small molecule 3F1 which was capable of selectively dispersing S. mutans biofilms and utilized it to determine whether selective targeting of S. mutans biofilms could effectively prevent dental caries and preserve the oral microbiome. We identified small molecule 3F1 capable of selectively dispersing S. mutans biofilms in vitro. Dispersal by 3F1 was independent of known factors essential for biofilm development. In a rat caries study, treatment of rat molars for 4 weeks with 3F1 controlled S. mutans and prevented dental caries while preserving the oral microbiome. These results indicate that a S. mutans biofilm specific small molecule is a viable therapy to prevent dental caries without disturbing the oral microbiome. In order to persist in the oral cavity and cause disease, S. mutans must survive against toxic metal ions and antagonistic commensal species. Toxic levels of copper may result from amalgam and dietary intake. Imperative to survival against copper is the copper-resistance operon copYAZ. Evidence from copYAZ operon homologues in bacterial pathogens suggests that the components may play a role in fitness and virulence in S. mutans. Although the intact copYAZ operon has been implicated in copper-independent processes, the role of individual genes of the copYAZ operon in virulence has not been previously investigated. In this study, we elucidated the role of individual genes in the copYAZ operon in S. mutans virulence. In this study we demonstrated that only CopZ and not the CopYAZ operon plays a role in biofilm formation, expression and secretion of glucosyltransferases, and competitiveness against oral commensal species. Elucidation of the mechanism of copZ on the role of biofilm formation and competitiveness may lead to the identification of novel virulence-regulatory pathways that are amenable to drug discovery.

Share

COinS