Date of Award

2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Cell and Molecular Biology

Department

Cell & Molecular Biology

First Advisor

Matthew Ramsey

Abstract

The human oral cavity is a complex polymicrobial environment, home to an array of microbes that play roles in health and disease. Oral bacteria have been shown to cause an array of systemic diseases and are particularly concerning to type II diabetics (T2D) with numerous predispositions that exacerbate bacterial infection. In this dissertation, we investigated the serum of healthy subjects and T2D subjects to determine whether we see greater translocation of oral bacteria into the bloodstream of T2D individuals. We didn’t observe any significant enrichment of oral taxa, however we detected the presence of an emerging pathogen, Acinetobacter baumannii that is also associated with impaired inflammation in T2D.

While some are associated with disease, many oral taxa are important in the prevention of disease. In this dissertation we investigated the interactions between two abundant health-associated commensal microbes, Haemophilus parainfluenzae and Streptococcus mitis. We demonstrated that H. parainfluenzae typically exists adjacent to Mitis group streptococci in vivo in healthy subjects. We revealed that this co-occurrence is density dependent and further influenced by H2O2 production. Additionally, Mitis group streptococci are likely the in vivo source of NAD for H. parainfluenzae further facilitating this co-occurrence. We also investigated H. parainfluenzae’s response to H2O2 which is composed of a redundant OxyR-controlled system. Furthermore, we showed that H2O2 likely elicits the SOS response in H. parainfluenzae which may be a mechanism of generating genetic diversity within this species. These findings reveal mechanisms behind why these two highly abundant taxa coexist in healthy individuals.

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